Aitken, Leanne M. RN, PhD, FRCNA; Williams, Ged RN, MHA; Harvey, Maurene RN, MPH; Blot, Stijn RN, Cc, RN, MNSc, PhD; Kleinpell, Ruth RN, PhD; Labeau, Sonia RN, MNSc; Marshall, Andrea RN, PhD; Ray-Barruel, Gillian RN, Grad Cert ICU Nursing, BA (Hons); Moloney-Harmon, Patricia A. RN, MS, CCNS, FAAN; Robson, Wayne RN, MSc; Johnson, Alexander P. RN, MSN, ACNP-BC, CCNS, CCRN; Lan, Pang Nguk RN, MSc; Ahrens, Tom RN, DNS, FAAN
Sepsis, including severe sepsis and septic shock, continues to be a major healthcare problem internationally. Although mortality related to severe sepsis and septic shock have reduced slightly in the past decade, it remains >20% (1, 2). As part of the response to optimize care for this group of patients, evidence-based clinical practice guidelines have been published by the Surviving Sepsis Campaign (SSC) to facilitate clinicians to improve the outcomes of patients with sepsis and septic shock (3, 4).
Although the SSC guidelines (4) provide a comprehensive review of the medical management of patients with sepsis and septic shock, they are frequently silent on the nursing care that is essential for optimal outcome of these patients. Expert nursing knowledge and skill are required for both the identification of the deteriorating patient as a result of newly developed sepsis and the ongoing implementation of competent care for the known severe sepsis patient. The World Federation of Critical Care Nurses, as the premier organization for critical care nurses worldwide, consequently formed an international group of interested experts in the area to provide guidance for nursing care of severe sepsis patients.
This care is provided by every registered nurse, as well as many of the advanced practice nurses (e.g., Nurse Practitioner, Clinical Nurse Specialist, or Consultant) who practice in the acute hospital setting. Internationally, advanced practice nursing roles vary in scope, education, and authorization. Although the scope and requirements for some of these roles are designated by legislation, for example, the scope of practice of the nurse practitioner, many of the roles are professional extensions of the registered nurse role. Given this variation in nursing roles from one region or country to another, we have not attempted to limit the recommendations contained within this document to care provided only by registered nurses, but have extended it to cover the practice of all nurses, regardless of their specific role.
Most of these recommendations relate to the adult septic patient, with the majority of interventions not tested in the pediatric patient. Despite this, many of the recommendations are likely to be applicable to the pediatric setting. Throughout the document, we have identified where specific information confirming or denying application to patients in specific age groups exists. Recommendations specific to the pediatric septic patient are contained within a section later in the article.
Although this article is designed to provide guidance for every nurse who cares for patients with severe sepsis, we also have provided recommendations regarding practice in areas of joint responsibility with other members of the healthcare team. For example, nurses frequently influence which central venous catheters or endotracheal tubes are purchased and used, as well as provide care related to the device after insertion. In addition, although most nurses do not order drugs, they do participate in protocol development and often advocate for the timely ordering and administration of medications important to patient outcomes in severe sepsis. Consequently, it is essential that nurses are familiar with the best available evidence.
Of note, this document is not designed to provide information regarding strategies for implementation to ensure practice is based on these recommendations. Rigorous and comprehensive implementation and evaluation strategies are essential but constitute a separate body of knowledge and as such are not reviewed in this document. Clinicians are encouraged to become familiar with appropriate strategies before implementing the recommendations outlined throughout this document. Therefore, the aim of this review is to provide a series of recommendations, based on the best available evidence, to guide clinicians providing nursing care to patients with severe sepsis.
Sepsis, including severe sepsis and septic shock, has been well-defined in the literature and inform these guidelines (Table 1). These guidelines for nursing care are designed to augment, not to replicate or replace, the current SSC guidelines (4) and have been developed using the following methodology: World Federation of Critical Care Nurses formed a team to develop guidelines for the nursing care of patients with sepsis; the organization appointed a coordinator (L.M.A.) and an organizational sponsor (G.W.); known experts in the field of sepsis care were invited to contribute to the guidelines; authors worked in subgroups of two or three; whenever possible, these authors represented different geographical regions of the world; the broad structure of the SSC guidelines (4) was used to inform the structure and content of these guidelines for nursing care; an additional section relating to prevention of infection and subsequent sepsis was added in recognition of the pivotal role that nurses provide in this area; each subgroup of authors undertook searches to locate any published literature that informed the nursing care of patients with severe sepsis; authors searched the literature referred to in the SSC guidelines (4), with searches expanding based on the section topics; analogous to the SSC guidelines (4), the Grades of Recommendation, Assessment, Development, and Evaluation (GRADE) system (5) was used to rate the quality of the evidence (Table 2); initial discussion of relevance and quality of the evidence was undertaken electronically within the subgroups; all recommendations were reviewed by the coordinator as well as an independent reviewer (G.R.B.), and queries were discussed electronically with the subgroup and then with the entire author team when necessary; the evidence supporting each recommendation, as outlined in the rationale, and the associated level of recommendation, was then forwarded to all authors who confirmed, or not, their support for each recommendation based on the rationale and summary of evidence in line with the GRADE system (5); and every recommendation that did not receive 100% agreement for the grade of support was subject to e-mail discussion and exploration of additional evidence until consensus by all members of the author team was achieved.
This project was conducted under the auspices of the World Federation of Critical Care Nurses, and no sponsorship or funding was received for this project. All authors report no conflict of interest with respect to the clinical recommendations or consensus-based evidence ratings.
I. INFECTION PREVENTION
1. We recommend interactive, multifaceted, longitudinal educational programs and educational outreach to enhance guideline implementation. Traditional education approaches, such as incorporated passive education and information dissemination through conferences, web sites, and didactic lectures, are often not effective (grade 1A).
2. We recommend educational initiatives to reduce healthcare-associated infection rates (grade 1C).
Education is generally considered as a first step to increase awareness of a problem and as crucial for processes of change. A systematic review found that interactive, multifaceted, longitudinal educational programs and educational outreach enhance guideline implementation (6). More specifically, a systematic review that investigated the effect of education on the reduction in infection rates concluded that the implementation of educational interventions may considerably reduce healthcare-associated infections (7).
1. We suggest the promotion of a culture of patient safety and individual accountability (grade 2D).
Recent trends have seen a transition from accepting healthcare-associated infection as an inevitable outcome of admission to the intensive care unit (ICU) (8) toward personal accountability and a goal of zero tolerance in relation to hospital-acquired infections (9, 10). A systematic review of 30 reports of nosocomial infection found that at least 20% could be preventable (11). A major impediment to achieving zero tolerance toward hospital-acquired infection has been a lack of accountability of all levels of hospital staff (9). This attitude is shifting, with recognition that hospital management and every healthcare worker are responsible and accountable for ensuring patient safety, including infection prevention and control (9, 10). Educating and empowering nurses to ensure infection control guidelines are followed by all staff has the potential to positively impact on hospital-acquired infections (12, 13).
C. Surveillance of Nosocomial Infections
1. We recommend a continuous surveillance program for the detection of nosocomial infection (grade 1B).
Local surveillance systems (eventually integrated in a national surveillance program) allow benchmarking of nosocomial infection data and therefore are essential to guide and evaluate interventions to reduce infection rates. Surveillance systems combined with appropriate feedback contribute to reduced nosocomial infection risk (14–19).
D. Hand Hygiene
1. We recommend hand antisepsis, irrespective of the use of gloves, between caring for different patients or between different care activities for the same patient, immediately before and after each episode of direct patient contact, and after any activity or contact that potentially results in hands becoming contaminated (grade 1B).
2. We recommend hand antisepsis by means of an alcohol-based hand rub (grade 1A).
3. We recommend washing hands with soap and water when hands are visibly soiled (grade 1A).
4. We recommend the use of gloves when contact with blood or other potentially infectious materials, secretions, mucous membranes, and nonintact skin could occur (grade 1D).
Adequate hand antisepsis has proven to result in reduced infection rates (20, 21). The use of alcohol-based hand rub is particularly effective; in contrast with hand washing, it kills susceptible bacteria more rapidly and to a greater extent, is less time-consuming, and skin health is better preserved when moisturizers are added. Hand disinfection after glove removal is necessary because gloves may have imperceptible defects or may be torn during use, resulting in contamination of hands. Hand washing is necessary when hands are visibly dirty because alcohol-based hand rub is ineffective in the presence of organic material. However, after hand washing, the use of alcohol-based hand rub remains mandatory (20, 21).
As a rule of thumb, a first step toward adequate hand hygiene consists of avoiding direct contamination of hands. The use of nonsterile, well-fitting gloves is recommended whenever the risk of contamination exists. Gloves must be changed between separate tasks on one patient (when going from a dirty/contaminated to a clean body site) and in between different patients (20–22).
E. Site-Specific Considerations
Most healthcare-associated infections in the ICU are related to the use of therapeutic devices. These include ventilator-associated pneumonia (VAP), catheter-related bloodstream infection (CR-BSI), surgical site infection (SSI), and urinary tract infection (UTI) (23, 24). Recommendations for their prevention are outlined.
E1. Prevention of Respiratory Infections
The development of pneumonia in patients mechanically ventilated with an artificial airway may affect 10% to 48% of patients (25–27). VAP is associated with a higher mortality rate and significantly longer ICU length of stay and hospital costs (24, 27). However, VAP is often preventable, and application of practices such as education strategies (28, 29) and ventilator bundles (30, 31) have contributed to a reduction in VAP incidence. Strategies to prevent VAP should be considered in all patients with severe sepsis (32).
1. We recommend head-of-bed elevation 30 to 45 degrees for all critically ill and mechanically ventilated patients (grade 1B). Special attention should be given to maneuvers in which it is difficult to achieve a 30-degree head-of-bed elevation, such as during bed bath or changing sheets. In such circumstances, we recommend back-rest elevation of at least 10 degrees should be maintained.
Aspiration of upper airway secretions is a common event even in normal healthy adults (33). Semirecumbent position in mechanically ventilated patients has been associated with lower levels of aspiration into the lower airways (34–36) and lower VAP incidence than the supine position (37–39). In patients receiving enteral nutrition, head-of-bed elevation is especially effective in reducing the risk of VAP (37). However, the feasibility of maintaining head-of-bed elevation in daily practice has been questioned by some authors (40, 41). Van Nieuwenhoven et al (41) achieved average head-of-bed elevation of only 28 degrees despite a target of 45 degrees, whereas Song et al (40) achieved head-of-bed elevation >30 degrees in 43.4% of patients.
2. We recommend the use of an endotracheal tube with subglottic secretion drainage in patients expected to require mechanical ventilation for >72 hrs (grade 1A).
Impaired gag reflex leads to pooling of secretions in the posterior part of the oropharynx (42), with microaspiration of subglottic secretions leading to VAP. Subglottic secretion drainage is accomplished through use of a specially designed endotracheal or tracheotomy tube with a separate dorsal lumen that opens directly above the endotracheal tube cuff. Subglottic secretions drainage appears to be effective in preventing VAP (relative risk, 0.51; 95% confidence interval [95% CI], 0.37–0.71) in patients expected to be mechanically ventilated for >72 hrs (43).
3. We suggest the use of a silver-coated endotracheal tube be considered (grade 2A).
In multicenter, randomized, controlled trials, a silver-coated endotracheal tube was demonstrated to reduce bacterial airway colonization as well as VAP in patients intubated 24 hrs or more (44, 45). More studies that confirm the current findings are required.
4. We suggest the use of an endotracheal tube with a polyurethane cuff (grade 2B).
In a single-center, randomized, controlled trial, an endotracheal tube with a polyurethane cuff was shown to significantly reduce early-onset postoperative pneumonia in cardiosurgical patients (46). More studies that confirm this result are required.
5. We recommend endotracheal cuff pressure be maintained at least 20 cm H2O, but not >30 cm H2O (grade 1C).
Inadequate cuff pressure is a risk factor for microaspiration of oropharyngeal secretions and subsequent pneumonia. One observational study among intubated patients not receiving antibiotic therapy showed that a persistent intracuff pressure <20 cm H2O was an independent predictor of VAP (relative risk, 4.2; 95% CI, 1.1–15.9) (47). Cuff pressure should be maintained at the lowest pressure >20 cm H2O that prevents cuff leak.
6. We suggest heat and moisture exchangers should be changed between patients, every 5 to 7 days, or as clinically indicated (grade 2C).
Humidification of inspired air to prevent mucosal injury may be achieved by using a heated humidifier, a heated humidifier with a heated wire circuit, or passively using a heat and moisture exchangers. There are insufficient data to demonstrate a benefit in VAP reduction for any humidification device (48). No benefit in infection rates or functionality of ventilator circuits has been demonstrated when heat and moisture exchangers are changed every day compared to every 5 to 7 days (49, 50).
7. We recommend ventilator circuits should not be changed routinely, except between patients (grade 1B).
There is no evidence that routine ventilator circuit changes can reduce the incidence of VAP (25, 51). New ventilator circuits should be used for each patient, and circuit changes should be performed only if the circuit becomes visibly soiled or damaged (32).
8. We recommend the aspiration of endotracheal secretions in response to clinical signs, i.e., visible or audible signs of respiratory secretions, respiratory deterioration, or other changes in the patient's condition that may be attributable to respiratory secretions in intubated patients (grade 1C).
Critically ill patients mechanically ventilated via a tracheal tube frequently require removal of tracheobronchial and upper airway secretions because of increased mucus production and a decreased ability to clear secretions (52, 53). Secretion removal may reduce infectious, respiratory, and tube patency complications (54–56).
Suctioning should only be performed when necessary, using the lowest possible suction pressure, take no longer than 15 secs, and use continuous rather than intermittent suctioning; the suction catheter should occlude less than half the lumen of the endotracheal tube and be inserted no further than the carina; hyperoxygenation should be provided before and after suctioning; and saline lavage should be avoided (55, 57).
The optimum frequency of endotracheal suctioning has not been clearly determined but should be in response to clinical signs (56). There is insufficient evidence to recommend the benefits of either an open or closed suctioning system (57).
9. We recommend regular mouth care and oral cavity assessment be provided to all critically ill and intubated patients (grade 1C).
Colonization of the oropharynx by pathogens is a potential risk factor for the development of VAP (58–60). Critical illness contributes to changes in the oral flora, and an increase in Gram-negative flora that includes more virulent organisms may occur (61, 62). Providing regular oral care, incorporating oral cavity assessment, is an important part of providing comfort to the critically ill patient (63) and is also demonstrated to contribute to a decrease in VAP (63–67). Assessment should include the condition of the teeth, gums, tongue, mucus membranes, and lips, and barriers to mouth care delivery (63). The use of a designated oral care protocol, in association with an education program for nurses in its importance in preventing VAP, can increase compliance and assessment of mouth care (68).
10. We recommend the use of chlorhexidine-based antiseptic for oral care in intubated patients (grade 1A).
Chlorhexidine is widely used and investigated in the oral care of intubated patients (69–72). Chlorhexidine effectively decontaminates the oropharynx (73, 74), and its use in oral care has been proven to decrease dental plaque (75) and incidence of respiratory infections (76), and to substantially decrease the incidence of VAP (77–79). The optimal concentration of chlorhexidine solution (0.12%, 0.2%, or 2%) remains undetermined. The optimum frequency for oral care with chlorhexidine has not been demonstrated. In general, a frequency of three to four times daily is proposed (69, 80, 81). The benefit of tooth brushing in critically ill patients as a component of oral care protocols has demonstrated efficacy, but additional research is indicated (65, 66). Tap water is not recommended for oral care in the critically ill (63).
E2. Prevention of CR-BSI
1. We recommend the implementation of a central line care bundle, including staff education, creation of a catheter insertion cart, implementation of a checklist to ensure adherence to evidence-based guidelines, empowering nurses to stop catheter insertion procedures when a guideline violation is observed, and daily assessment of possible catheter removal (grade 1B).
A bundle approach to central venous catheter (CVC) insertion and care (12, 13, 82, 83) has proven to be effective in substantially reducing the rate of CR-BSI. Nurses play a key role in preventing CR-BSI through these activities outlined.
2. We recommend the use of maximal sterile barriers during CVC insertion (grade 1A).
During the CVC insertion procedure, all healthcare personnel involved must wear a mask, cap, sterile gown, and sterile gloves, and the patient is to be covered with a large sterile drape (84–88). Use of maximal sterile barrier precautions during CVC insertion have led to reduced infection rates (87, 89, 90).
3. We recommend the use of a chlorhexidine-based antiseptic for skin preparation before insertion and subsequent catheter care (grade 1A).
Because the risk of CR-BSI increases with the density of microorganisms at and around the insertion site (21), site antisepsis is crucial in the prevention of infection. Aqueous chlorhexidine (2%) solution consistently has been found to be superior to both 10% povidone iodine and 70% alcohol for preventing CR-BSI (91–93).
4. We suggest the replacement of administration sets every 96 hrs (grade 2A), except when used for the administration of blood, blood products, or lipids, in which case sets must be changed within 24 hrs (grade 1A).
A Cochrane systematic review found no increase in the risk for CR-BSI when the interval for administration set replacement was increased from 72 hrs to 96 hrs (94). When a fluid that enhances microbial growth is infused (lipid emulsions, blood products), more frequent changes of administration sets are indicated because these products have been identified as independent risk factors for CR-BSI in both adults and neonates (95–100).
5. We recommend the use of minocyclin-rifampin impregnated catheters (grade 1B).
Studies have repeatedly demonstrated a significant reduction in CR-BSI with the use of impregnated CVCs in comparison with standard catheters (101–104); this reduction in infection rates has been greatest with minocycline-rifampin–coated CVCs when compared to other impregnated CVCs (105). Minocycline-rifampin impregnated CVCs are approved for use in the pediatric population by the Food and Drug Administration (United States); however, studies have not been conducted in children.
E3. Prevention of SSI
1. We recommend that antimicrobial prophylaxis be administered within 1 hr before incision to maximize tissue concentration. Two hours are allowed for the administration of vancomycin and fluoroquinolones (grade 1A).
In 2003, the Surgical Infection Prevention Guideline Writers Workgroup meeting reviewed the various guidelines for antimicrobial prophylaxis in surgery (106). On the basis of published evidence, the workgroup concluded that infusion of the first antimicrobial dose should begin within 60 mins before incision, and when a fluoroquinolone or vancomycin is indicated the infusion should begin within 120 mins before incision to prevent antibiotic-associated reactions (106, 107).
2. We recommend that only hair that will interfere with the operation be removed, and that if hair removal is necessary, then it should be removed by using electric clippers (grade 1B).
Although several authors have reported preoperative hair removal is associated with increased SSI rates (108–111), a Cochrane systematic review compared a variety of hair removal methods (depilatory cream, razors, clippers) vs. no hair removal and reported no difference in SSI rates among patients who had hair removal before surgery and those who did not (112). The same review found that shaving led to statistically significantly more SSIs compared with clipping or depilatory cream (112). The increased infection risk associated with the technique of shaving is attributed to the formation of microscopic cuts in the skin that later act as foci for bacteria (108). Although the use of depilatories has been associated with a lower SSI risk than shaving or clipping (113, 114), they can produce hypersensitivity reactions (114).
3. We recommend that blood glucose levels be controlled during the immediate postoperative period for patients undergoing cardiac surgery: controlled blood glucose level (<200 mg/dL) on postoperative day 1 and postoperative day 2, with procedure day being postoperative day 0 (grade 1C).
Increased glucose levels (>200 mg/dL) in the immediate postoperative period (≤48 hrs) are associated with increased SSI risk (115, 116). One study found that patients with a blood glucose level >300 mg/dL within 48 hrs of surgery had more than three-times the likelihood of a wound infection (117). Regular monitoring of glucose levels and timely administration of insulin and hyperglycemic agents are direct nursing responsibilities; therefore, nursing education should stress the importance of glucose control in preventing SSI.
4. We recommend the identification and treatment of infections remote to the surgical site before elective surgery (grade 1B).
Concurrent remote site infections are considered to increase SSI risk (118–120). Therefore, whenever possible, all infections remote to the surgical site should be identified and treated before elective operation, and elective operations on patients with remote site infections should be postponed until the infection has resolved (108).
E4. Prevention of UTI
1. We recommend that all attempts should be made to limit the duration of urinary catheterization (grade 1C).
The urinary tract is the most prevalent source of nosocomial infection and there are several recommendations to prevent or reduce the incidence of UTI (121). Duration of catheterization is the most important risk factor for development of UTI (121). Postoperative urinary catheterization >2 days is associated with an increased likelihood of UTI and 30-day mortality, as well as a decreased likelihood of discharge to home (122). Nurses should advocate for prompt removal of urinary catheters (123) and discourage long-term catheterization, if possible.
2. We recommend that a sterile, continuously closed drainage system be maintained (grade 1A).
Closed urinary drainage systems are pivotal in preventing UTI (21, 123). The risk of infection reduces from 97% using open systems to 8% to 15% when sterile closed systems are used (124–126). Errors in maintaining sterile closed drainage and opening the closed drainage system have been well-documented to predispose patients to infection (124, 126–129).
3. We recommend regular perineal hygiene measures (grade 1C).
Most episodes of UTI are caused by the patient's own flora (121). Daily cleansing of the urethral meatus using soap and water or perineal cleanser is recommended (123, 130).
4. We suggest the maintenance of unobstructed urine flow (grade 2C).
Reflux of urine is associated with infection; therefore, drainage bags should be positioned below the level of the bladder at all times to prevent urine back-flow and unobstructed urine flow should be maintained (21, 131, 132).
II. Infection Management
A. Infection Source Control Issues
1. We recommend prompt removal of intravascular catheters and subsequent catheter tip culturing in patients with proven bloodstream infection associated with severe sepsis as well as in hemodynamically unstable patients with suspected CR-BSI (grade 1C).
Prompt removal of contaminated invasive devices is a cornerstone in the management of device-related infection. Failure to remove the catheter was demonstrated to be an independent predictor of mortality in an epidemiologic study on CR-BSI (odds ratio, 0.22; 95% CI, 0.10–0.86) (133). If the catheter is removed for suspected CR-BSI, then guide wire exchange is acceptable in circumstances in which catheter insertion is problematic because this reduces the risk for mechanical complications (134). If, however, the catheter tip culture appears to be positive, the newly inserted catheter should be replaced a second time because bacterial contamination can be expected and guide wire exchange on itself was shown to be an independent risk factor for the development of CR-BSI in an observational study (odds ratio, 4.59; 95% CI, 2.28–9.3) (133).
B. Transmission-Based Precautions
1. We recommend transmission-based precautions for patients who are known to be or are suspected to be infected or colonized with infectious agents, including certain epidemiologically important pathogens (grade 1A).
Standard precautions are required for all patients. In addition, patients colonized or infected with epidemiologically important pathogens, including methicillin-resistant Staphylococcus aureus; vancomycin-resistant enterococci, glycopeptide-resistant Staphylococcus aureus, extended-spectrum β-lactamase producing Enterobacteriaceae, multidrug-resistant nonfermenting Gram-negative bacteria, and Clostridium difficile may pose a potential threat to patients in their vicinity (135) and require additional precautions to prevent cross-infection. There are three categories of transmission-based precautions: contact, droplet, and airborne precautions (136). For diseases with multiple routes of transmission, more than one transmission-based precautions category may be recommended. Transmission-based precaution categories and the particular measures they include are described in detail elsewhere (136).
III. INITIAL RESUSCITATION
Because the SSC guidelines (4) for initial resuscitation (6-hr resuscitation bundle) are operational only from the point that severe sepsis/septic shock is diagnosed, the processes that lead to early diagnosis are pivotal. Many of the processes that support compliance with the 6-hr resuscitation bundle such as recording and interpreting clinical observations, seeking further assistance, and initiating early resuscitation measures are often the domain of nurses. The role of the nurse in initial resuscitation will vary according to the clinical area concerned. On a general ward, nurses will be responsible for monitoring clinical observations and administering antibiotics and fluid challenges, whereas in a critical care area nurses may be also be involved in monitoring hemodynamic status and administering vasoactive agents. The nurse's role in initial resuscitation does not end when medical staff members arrive on the scene. Successful resuscitation depends on collaborative integration of the skills and expertise of all members of the multidisciplinary team.
A. Recognizing Deterioration and Diagnosing Severe Sepsis
1. We recommend that all staff with a direct responsibility for patient care (including nursing assistants and healthcare assistants) be educated to recognize the Systemic Inflammatory Response Syndrome (SIRS) criteria and signs of severe sepsis or septic shock (grade 1C).
All staff with a direct responsibility for patient care, including the taking of vital signs, must be able to recognize the clinical findings of SIRS and sepsis (Table 3). The definitive diagnosis of sepsis or severe sepsis in hospital patients will often be made by a medical officer, but the clinical review leading to diagnosis usually will be facilitated by a nurse who recognizes signs and symptoms indicative of the onset of SIRS or sepsis or both (137).
Nurses therefore play a pivotal role in the early identification of deteriorating patients and prompt management of sepsis to enhance recovery (138). Numerous studies have demonstrated the relationship between nursing and failure-to-rescue (139, 140). The effect on patient outcomes of providing sepsis education for all nurses including nursing assistants is inconclusive. A national sepsis education program in Spain for medical and nursing staff marginally improved guideline compliance and hospital mortality rates (44.0% vs. 39.7%; p = .04) but did not demonstrate sustained improvement after 1 yr (141). However, a more recent multi-national performance improvement study demonstrated sustained improvement in both compliance and patient mortality at 2 yrs (142).
2. We recommend the use of early warning systems (EWS) to assist in the early recognition of sepsis to promote prompt treatment to enable best patient outcomes (grade 1C).
3. We suggest the use of sepsis screening tools to assist in the early recognition of sepsis to promote prompt treatment to enable best patient outcomes (grade 2C).
Early diagnosis of sepsis is linked to improved outcomes and survival from sepsis. The recognition of patient deterioration and diagnosis of sepsis relies on the detection of abnormalities in physiologic data. The collection and documentation of clinical observations is an important nursing role (143, 144). Despite this, there is evidence that clinical observations sometimes are performed poorly or not at all, are not documented, are not interpreted correctly, or are not reported when abnormalities are found (145). EWS, also known as track and trigger systems, have been promoted to aid in the detection of deterioration by highlighting abnormalities in clinical observations (146); however, the evidence of their effectiveness is inconclusive (147, 148). Additional verification of the usefulness of EWS is needed to recommend consistent use in clinical care.
The addition of sepsis screening tools have been recommended in promoting early recognition of patients at risk for development of or those who have SIRS criteria, indicating the early onset of severe sepsis (146, 149). Sepsis screening can be added to observation charts or EWS charts, prompting nurses to use a sepsis screening tool if the patient triggers one or more of the SIRS criteria of temperature, heart rate, and respiratory rate (149). One study reported a decrease in mortality of one-third after the introduction of a three-step sepsis screening tool (150).
B. Seeking Further Assistance
1. We suggest that communication tools (e.g., Situation, Background, Assessment, Recommendations [SBAR] and Reason, Story, Vital Signs, Plan [RSVP]) be used to improve communication and promote prompt identification and treatment of patients with suspected or confirmed sepsis (grade 2D).
Summoning medical assistance is crucial in implementing the resuscitation bundle, and communication delays can result in poorer outcomes for patients with severe sepsis. There is evidence that nurses and medical staff do not always communicate effectively with each other (145, 151). Communication between disciplines can be improved by using structured communication tools such as SBAR (152, 153), RSVP(154), and EWS (155) that incorporate objective, unambiguous language to convey patient information. Sepsis screening tools may also be incorporated into the assessment (SBAR) or vital signs (RSVP to ensure the nurse cogently relays the message that the patient meets the consensus definition for severe sepsis and needs immediate attention to implement the resuscitation bundle.
C. Initiating Early Resuscitation Measures
1. We suggest that the initial resuscitation of patients with sepsis be provided through the use of rapid response systems (grade 2B).
Early recognition of sepsis can improve patient outcomes if a rapid response is initiated (156, 157). Early goal-directed therapy (EGDT) and the SSC guidelines have demonstrated efficacy in improving mortality outcomes in severe sepsis (4, 158, 159). Despite this, compliance with the 6-hr resuscitation bundle is poor, ranging from 19% to 52% (160, 161). A number of studies have explored the poor uptake of EGDT and suggest barriers to implementation include inadequate facilities (162) and inadequate numbers of nurses (163).
Nurses must be able to recognize signs of severe sepsis and be knowledgeable about the 6-hr bundle components to begin prompt implementation of therapy. The focus then should be on identifying patients eligible for EGDT (those not responding to fluid resuscitation or having a lactate >4 mmol/L or both) and arranging prompt transfer to a higher level of care area such as the high-dependency unit and ICU to ensure timely treatment for severe sepsis. Table 5 outlines additional strategies for integrating the SSC guidelines in nursing practice (138).
2. We suggest the provision of adequate resources to enable prompt identification of patients with actual or suspected sepsis (grade 2D).
A recent U.K. survey of acute medical units found that only 12% appeared to have the minimum facilities to comply with the 6-hr resuscitation bundle (162). Performing EGDT can be labor-intensive and may require a minimum of two nurses in the initial phase (164), although some clinical settings can incorporate EGDT into their regular clinical duties without the allocation of additional staff (165). Recommended resources include arterial blood gas monitors, and laboratory facilities for measuring lactate levels such as serum lactate have been demonstrated to be an independent predictor of mortality in patients with severe sepsis (166). Hand-held lactate monitors should be available in noncritical care areas to help identify those with cryptic shock (raised lactate in the absence of hypotension) who otherwise may be overlooked.
3. We recommend that adequate nurse staffing levels be ensured to provide quality patient care and improved patient outcomes (grade 1B).
The impact of registered nurse staffing levels on patient outcomes is well-documented, with lower nurse-to-patient ratios being associated with higher rates of pneumonia (167–171), shock, UTI (169), upper gastrointestinal bleeding, deep vein thrombosis, cardiac arrest, and failure to rescue, as well as infection (172) and sepsis (167, 168, 170, 173–176). Nurse-to-patient ratios in ICUs in the United States and some parts of Europe typically range from 1:1 to 1:3, depending on patient acuity levels, whereas in countries such as Australia, New Zealand, and the United Kingdom, ratios are 1:1 because of not having personnel such as respiratory therapists to assist in the management of acute and critically ill patients. Nurse-to-patient ratios of one nurse caring for one or two patients (≤1:2) vs. one nurse caring for three or more patients (> 1:2) in the ICU have been found to be associated with increased risk of postoperative pulmonary and infectious complications (167).
4. We suggest that nurses be empowered to initiate the 6-hr resuscitation bundle. All nurses should be trained to take blood, cannulate, and administer intravenous fluids via standing orders for hypotension or increased lactate or both (grade 2C).
5. We suggest that the sepsis six approach be promoted in noncritical care areas to promote early identification and treatment of severe sepsis (144) (grade 2D).
Although nurses may identify signs of severe sepsis, they may be unable to initiate the resuscitation bundle interventions such as administering antibiotics and fluid boluses without a specific physician order. Standing order sets and established protocols have been utilized to facilitate early implementation of the bundle components (177).
In the United Kingdom, poor uptake of EGDT in emergency departments (178) led to a change in focus on education to concentrate on care that could be delivered by staff without specialist skills and equipment in the first hour after diagnosis. This has been called the sepsis six and includes six crucial interventions in sepsis resuscitation, including starting high-flow oxygen, obtaining blood cultures, administering antibiotic therapy, starting intravenous fluid resuscitation, obtaining laboratory work including hemoglobin and lactate levels, and measuring hourly intake and output (144, 159, 179) (Table 4). Nurses play an important role in each of these interventions. High-flow oxygen therapy is not currently included in the SSC guidelines (4) but is universally recommended as being an important aspect of resuscitation of the critically ill and should be initiated by nurses (180, 181). Many nurses perform venipuncture and can rapidly obtain blood for cultures and venous lactate assessment, or can ensure equipment is available promptly if they are unable to perform venipuncture.
Because a medical officer may not be always readily available, some hospitals have introduced measures to empower nurses to administer fluid challenges for hypotensive patients via standing orders or patient group directions to reduce delays in patients receiving fluid resuscitation (182). Protocol-directed care in the areas of fluid and vasopressor therapy is becoming more commonplace and has been shown to be safe (177, 183). In the United Kingdom and the United States, advanced practice nurses independently prescribe medications and can initiate orders for sepsis management, thus helping to facilitate early resuscitation measures (184, 185). Including nurses who are able to prescribe antibiotics, fluids, and vasopressors on critical care outreach teams, rapid response system teams may also reduce delays in implementing the 6-hr bundle.
EGDT incorporates blood transfusion for some patients and is recognized as a serious threat to patient safety; nurses play an important role in ensuring that patients who require transfusion receive blood in a safe manner guided by best evidence recommendations (186, 187).
6. We recommend that supplies of commonly used, ready-mixed antibiotics should be available in all acute wards and departments (grade 1D).
Usually it is nurses who administer antibiotics after a medical officer has prescribed them. Unfortunately, antibiotic administration can be delayed up to 6 hrs in some patients with bloodstream infection (188, 189). Reasons for such delays include lack of intravenous access and the prescribed antibiotic not being available (188). Measures such as having commonly used antibiotics and ready-mixed antibiotics available, as well as training nurses to cannulate, should be considered (190).
7. We suggest the institution of tracking systems including the use of daily sepsis rounds in critical care areas (grade 2C).
Use of check sheets to monitor patients for signs of sepsis or automated computer-based sepsis alert programs (191) can enhance identification of patients with sepsis.
8. We suggest ER nurses should liaise with medical colleagues and prehospital staff to facilitate diagnosis and initial treatment of severe sepsis en route to hospital and to promote “alerting” of emergency departments that a patient with severe sepsis is expected (grade 2D).
This system is already common practice for patients with acute coronary syndrome and major trauma, and it may help to identify those patients eligible for EGDT (192).
9. We suggest further research on technology to aid the detection of sepsis (grade 2D).
Technology that alerts nurses performing clinical observations and calculation of EWS, such as Sepsis Alert, Biosign, Vitalpac, and others, is currently being developed by many different biotechnology companies. Evidence of the benefit of this trend is yet to be confirmed.
IV. HEMODYNAMIC SUPPORT
Hemodynamic monitoring techniques continue to develop and hemodynamic therapies for severe sepsis are essentially supportive care, aimed at improving both macrocirculation and microcirculation. The current SSC guidelines (4) are primarily based on an evidence-based practice guideline published in 2004 (193). Despite these excellent practice guidelines, questions remain in terms of the nursing care of septic patients with hemodynamic disturbances.
Complicating the care of patients with severe sepsis is the multimodal nature of the hemodynamics of sepsis. For example, in the early phase of sepsis, patients present with a relative hypovolemia that may be somewhat managed by restoring blood volume, i.e., restoring macrocirculation. However, as sepsis progresses, a disturbance that centers on the microcirculation is usually detected. At this point, the macrocirculation becomes hyperdynamic. Further treatment of the macrocirculation does little to address the problem of the microcirculation, e.g., microcirculatory clotting, cellular dysoxia, and cell stunning (194). The treatment for this latter stage is unclear.
Two key areas are developing in the management of the hemodynamics of severe sepsis (194). One focus is on improving tissue oxygenation, both in the macrocirculation and microcirculation. Hence, tissue oxygenation end points, such as central venous oxygen saturation (ScvO2), tissue oxygenation (StO2), and lactate are taking on increased importance. The second focus on treatment centers on improving macrocirculation, moving toward measuring flow rather than pressure.
A. Improving Tissue Oxygenation
1. We suggest continuous measurement of tissue oxygenation vs. intermittent measurement (grade 2D).
Central venous catheter use is associated with trends in mortality reduction as long as resuscitation bundle compliance exists (142). Continuous measurement of tissue oxygenation contributes to earlier recognition of changes in patient status and treatment efficacy in relation to periodic central line sampling. Whereas the cost of continuous ScvO2 monitoring technology is higher than the cost of processing intermittent samples, several factors mitigate this disadvantage. These factors include reduced nursing time with continuous measurement, avoidance of clinician exposure to blood, and improved ability to detect changes with continuous monitoring. Preliminary data suggest continuous ScvO2 monitoring may be more cost-effective for institutions overall (195).
2. We suggest consideration of noninvasive monitoring of tissue oxygenation when central venous access is less desired or unavailable (grade 2D).
Newer technology allows noninvasive monitoring of tissue (peripheral vascular) oxygenation, specifically near-infrared spectroscopy. StO2 is a continuous, transcutaneous measurement of tissue oxygenation via an electrode proximal to the thumb. Data suggest that StO2 may be a better marker than gross hemodynamics at revealing information regarding the microcirculation. Donati et al (196) showed that StO2 was responsive to identifying the impact of activated protein C, unlike gross measures of hemodynamics. Leone et al (197) indicated StO2 values <78% were correlated with lower survival rates. However, both of these studies were limited in both sample size and phase of sepsis utilized.
One of the main values of StO2 is its noninvasive application. Situations involving severe sepsis in which central venous catheter insertion is less desirable or inappropriate should be considered for StO2 monitoring. StO2 measurement can be obtained via an easy-to-use, transcutaneous application. Although not definitive at this point, some data suggest that below-normal values may identify sepsis earlier (198), predict development of organ dysfunction (199), and serve as an ScvO2 alternative. However, outcome data using StO2 are still lacking. Although promising, the literature remains unclear on how best to use StO2 in severe sepsis.
3. We suggest consideration of point-of-care lactate values as a quicker alternative to traditional serum lactate as appropriate (grade 2D).
Degree of blood lactate elevation correlates directly with morbidity and mortality in severe sepsis (200, 201), and high correlation also has been shown between central laboratory and point-of-care values. Early detection of elevated lactate facilitates early recognition and treatment in addition to being a more accurate triage tool than vital signs (201). Howell et al (201) indicated lactate would predict 28-day outcome better than traditional monitoring parameters such as blood pressure. Elevated lactate, specifically type A lactic acidosis, is one of the few indicators of hypoxia. Lactate can be at dangerous levels while normal monitoring parameters like vital signs remain within normal limits. Using point-of-care lactate as the catalyst to implementation of a sepsis algorithm, an 18% reduction in mortality and 4-day reduction in length of stay was achieved (202, 203). We suggest that point-of-care lactate measurement be considered to accelerate the clinician's knowledge of the danger a patient faces if serum lactate laboratory results exceed turnaround times of approximately 1 hr (200, 201).
B. Improving Macrocirculation
1. We suggest use of stroke volume or stroke volume variation as a key resuscitation measure, independent of whether a central line can be placed (grade 2D).
Improving blood flow is the key strategy during resuscitation. Secondary markers such as blood pressure, central venous pressure, and pulmonary capillary wedge pressure have been used as surrogates for blood flow (204). However, these parameters have been shown to be inaccurate and slow to change. More direct measures of blood flow, for example, stroke volume, offer more precise evaluation of the effectiveness of therapies such as fluids and inotropes (194). Although central venous pressure is recommended as a resuscitation end point in the SSC guidelines (4), clinicians must be aware of the limitations of treating right atrial pressure. Independent of sepsis, it is recognized that the usefulness of central venous pressure is limited in clinical decisions regarding fluid management because of inability to predict blood volume or preload in response to fluid resuscitation (205). Because central venous pressure was in both the intervention group and the control group in the original early goal-directed therapy article (158), one could argue that it was the added advantage of the ScvO2 in the intervention group that was associated with improved outcomes, i.e., not improving central venous pressure. The parameter that changes before ScvO2 is stroke volume. In the perioperative setting, measuring stroke volume has clearly shown to improve patient outcome (183, 206–213). Stroke volume optimization has been shown to be a much better metric of preload responsiveness compared to central venous pressure, blood pressure, and urine output. Even though data from the pulmonary artery catheter enable computation of a stroke volume estimate, more direct measurements of stroke volume are made possible by such innovations as the esophageal Doppler, noninvasive Doppler, and pulse contour techniques. A growing body of literature supports the efficacy of stroke volume optimization and stroke volume variation in sepsis (214, 215). Although the theoretical principle is clear, outcome studies using stroke volume and stroke volume variation for patients with sepsis are ongoing.
2. We suggest insertion of a peripherally inserted central catheter (PICC) in the event that subclavian central venous access cannot be obtained in patients with severe sepsis who meet the criteria for central line placement (grade 2D).
Enhanced catheter flow rates, hemodynamic monitoring, and power injection capability are among some of the most recent developments in peripherally inserted central catheter use. Additional advantages include the insertion capability of advanced practice nurses or trained registered nurses. Central venous pressure accuracy has been found to be similar when compared with a traditional central venous catheter (216). However, the ability of peripherally inserted central catheter to allow for ScvO2 measurement is perhaps its most distinct advantage compared to peripheral lines.
V. OTHER SUPPORTIVE NURSING CARE
All critically ill patients, including the patient with severe sepsis, should receive accepted standards of fundamental nursing care. Whereas no evidence specifically links many components of fundamental nursing care to the outcomes of patients with severe sepsis, these aspects of care have been shown to improve outcomes in all critically ill patients and a brief review follows. Many have been shown to reduce the risk of infection and therefore may decrease the risk of sepsis.
A. Nutrition Therapy
Critical illness is often associated with a hypermetabolic state and increased nutritional requirements. Malnutrition in the critically ill is not uncommon (217) and is associated with an increase in morbidity and mortality (218). Although the traditional emphasis of nutritional support has been on caloric intake, this has evolved to nutrition as a therapy in which the metabolic response to stress may be attenuated, cellular injury may be prevented, and the immune response may be favorably modulated (219). Extensive guidelines provide recommendations for nutrition therapy for the critically ill (217, 220–222) and have been shown to improve the provision of enteral nutrition (223). Consequently, incorporating such guidelines into the care of patients with severe sepsis is recommended.
1. We suggest early enteral nutrition (initiated within 24 to 48 hrs of ICU admission) (grade 2A).
Critical illness is associated with intestinal mucosal atrophy with loss of barrier function and potential microbial translocation. Early initiation of enteral nutrition may prevent intestinal mucosal atrophy. In addition, enteral nutrition can reduce the need for parenteral nutrition with substances that enhance bacterial growth (e.g., lipid emulsions) and, as such, reduce the risk of CR-BSI. Enteral nutrition, when compared to parenteral nutrition, has been shown to reduce the risk for infectious complications by 30% to 40% (224, 225). A similar reduction has also been found with early, compared to delayed, enteral nutrition (226). Despite the benefits of enteral nutrition, caution should be exercised in patients not yet resuscitated from septic shock when gut perfusion may be compromised. Caution should also be taken in using immune-modulating enteral formulations (supplemented with agents, such as arginine, glutamine, nucleic acid, omega-3 fatty acids, and antioxidants) in patients with severe sepsis (219).
B. Eye Care
1. We suggest daily assessment of the ability of the ICU patient to maintain eyelid closure (grade 2D).
2. We suggest at least weekly assessment of ICU patients for iatrogenic ophthalmologic complications and prompt referral for suspicion of these (grade 2D).
3. We recommend the maintenance of eyelid closure for intensive care patients (grade 1B).
These recommendations apply to all critically ill patients, including those with severe sepsis. Many critically ill patients have altered levels of consciousness, which may impact on the protective mechanisms of the eye, resulting in an increased risk of injury such as corneal dehydration, abrasion, perforation, and infection (227). The incidence of corneal abrasion varies widely but may affect up to 60% of intensive care patients (228–230). A variety of eye care methods have been described and tested, with evidence that a range of methods reduce the incidence of corneal damage (227, 230–232), but there is insufficient evidence to recommend any single method as being superior. Daily assessment of the patient's ability to maintain eyelid closure should be undertaken. Nurses could also be trained to perform weekly ophthalmologic examinations using fluorescein drops and a cobalt blue pen torch (231), because early detection of iatrogenic ophthalmologic complications will facilitate timely referral to ophthalmology specialists and potentially improve patient outcomes.
C. Pressure Ulcer Prevention and Management
1. We recommend the implementation of a pressure ulcer prevention and treatment bundle including risk assessment, skin assessment, nutrition, repositioning, and use of support surfaces (grade 1D).
Extensive recommendations for both the prevention and treatment of pressure ulcers have been developed and contain specific recommendations for the critically ill (233, 234).
Critically ill patients are susceptible to the development of pressure ulcers because of increased risks such as impaired circulation, use of inotropic drugs, decreased mobility, disturbed sensory perception, and underlying disease processes (235). The patient with severe sepsis often experiences significant hemodynamic compromise and therefore is particularly at risk for the development of pressure ulcers. Although variable, the incidence of pressure ulcers in the critically ill has been reported to be between 5.2% and 20%, with a prevalence rate of 14.4% (236). Whereas not all pressure ulcers can be avoided, strategies can be used to reduce the incidence. Assessment of risk factors is one such strategy, but the predictive validity of risk assessment scales is problematic and there is little evidence for a valid risk assessment tool in the critically ill (237–239).
Special considerations related to prevention include: use of special support surfaces for patients who cannot be turned regularly; slow, gradual turns, while assessing patient tolerance for the procedure, may reduce the effect on hemodynamic and oxygenation compromise; more frequent small shifts in position will allow some reperfusion in patients who cannot tolerate major shifts in body position; lateral rotation therapy may be considered. Patients receiving lateral rotation therapy will continue to require regular turns and skin assessment (233). Shear injury is a potential consequence of lateral rotation therapy. Bolster pads may prevent sacral shearing in these patients (233).
Special considerations related to management of pressure areas in severe sepsis patients include: positioning to minimize pressure on affected area; inspecting pressure ulcer and surrounding area with every dressing change; and, if there is evidence of shear injury, changing lateral rotation support to a support system with improved pressure redistribution, shear reduction, microclimate control, and without rotation (234). Documentation of pressure ulcer staging and treatment are essential for continuity of care; however, two recent systematic reviews revealed that a multitude of pressure ulcer grading scales currently exist, with insufficient evidence to recommend a specific classification system (240, 241). The role of ICU mobilization of critically ill patients also has been advocated for the promotion of skin integrity as well as prevention of complications of bed rest (242).
Sepsis remains an urgent issue among pediatric patients. Worldwide, it affects a large pediatric population and is the most common cause of death in infants and children (243). Severe sepsis accounts for >4300 deaths annually (244).
Sepsis tends to peak at two primary times in the child's life and corresponds to significant times in the maturity of the immune system (245). The first peak is in the neonate stage, with an incidence of 4.3 per 1000 neonates. Sixty percent of cases occur in the first 5 days, with an overall mortality of approximately 20%. The second peak is at approximately age 2 yrs.
In 2002, the International Pediatric Sepsis Consensus Conference participants modified the adult SIRS criteria and associated definitions for children (246). SIRS is defined as the presence of at least two of the following conditions, one of which must be abnormal temperature or leukocyte count. The conditions include: core temperature of >38.5°C or <36°C; tachycardia, defined as a mean heart rate >2 standard deviations above normal for age in the absence of external stimulus, chronic drugs, or painful stimuli or otherwise unexplained persistent elevation over a 30-min to 4-hr time period, or for children older than 1 yr of age, or bradycardia, defined as a mean heart rate below the tenth percentile for age in the absence of external vagal stimulus, β-blocker drugs, or congenital heart disease, or otherwise unexplained persistent depression over a 30-min time period; mean respiratory rate >2 standard deviations above normal for age or mechanical ventilation for an acute process not related to underlying neuromuscular disease or general anesthesia; and leukocyte count elevated or decreased for age (not secondary to chemotherapy-induced leukopenia) or the presence of >10% immature neutrophils (246).
An infection is defined as a suspected or proven (by positive culture, tissue stain, or polymerase chain reaction test) infection caused by any pathogen or a clinical syndrome associated with a high probability of infection. Evidence of infection includes positive findings on clinical examination, imaging, or laboratory tests (e.g., white blood cells in a normally sterile body fluid, perforated viscus, chest radiograph consistent with pneumonia, petechial or purpural rash, or purpura fulminans) (246).
Sepsis is defined as SIRS in the presence of or as a result of a suspected or proven infection (246). Severe sepsis is defined as sepsis plus one of the following: cardiovascular organ dysfunction; acute respiratory distress syndrome; and two or more other organ dysfunctions (respiratory, renal, neurologic, hematologic, hepatic) (246).
There are developmental differences in the hemodynamic response to sepsis in children when compared to adults. A decrease in cardiac output is associated with mortality in children with septic shock (247). Based on this developmental difference, reaching a therapeutic end point of a cardiac index of 3.3–6.0 L/min/m2 may result in better survival (247). In addition, oxygen delivery is the major determinant of oxygen consumption in children as opposed to oxygen extraction, so the therapeutic end point of an oxygen consumption of >200 mL/min/m2 also may be associated with a better outcome (247).
A. Fluid Resuscitation
1. We suggest intravascular volume expansion is achieved with fluid boluses of 20 mL/kg of isotonic saline or colloids, as identified in the SSC guidelines (4) (grade 2C).
As much as 200 mL/kg may be administered in the first hour of resuscitation, although the average is 40 to 60 mL/kg. Fluid replacement should be directed toward perfusion, central venous pressure, echocardiographic determination of end-diastolic volume, pulmonary capillary wedge pressure/end-diastolic volume, and cardiac output (247).
1. We suggest vasopressors/inotropes are implemented if clinical signs of shock continue despite adequate volume replacement, as identified in the SSC guidelines (4) (grade 2C).
An important point to remember about these medications is that because septic shock is a dynamic process, the medication used and the infusion dose may require adjustment over time, based on the need to maintain organ perfusion as well as the pharmacokinetics and the pharmacodynamics of the child's response to the drug. Perfusion and function of the liver and kidney are often changed in the child with severe sepsis, causing changes in the medication pharmacokinetics with higher concentrations observed. Therefore, standard infusion doses may need to be adjusted.
For ongoing therapy, the use of inotropes, vasopressors, and vasodilators will differ. Dobutamine may be useful for pediatric patients with low cardiac output states (248). Vasopressin can increase mean arterial pressure, systemic vascular resistance, and urine output in children with vasodilatory septic shock and lack of response to catecholamines. However, the safety and effectiveness of vasopressin in children with septic shock have not been well-demonstrated (249). Occasionally, children alter their hemodynamic requirements from vasopressor to inotrope or vice versa (247). Table 6 presents a summary of the pharmacologic therapy used in the treatment of pediatric septic shock (250).
1. We suggest hydrocortisone therapy may be generally reserved for the child with catecholamine-resistant shock and suspected or proven adrenal insufficiency, as identified in the SSC guidelines (4) (grade 2C).
Hydrocortisone therapy may be life-saving in the child with sepsis, but its use is generally reserved for the child with catecholamine-resistant shock and suspected or proven adrenal insufficiency. A recent study examined the issue of neuroendocrine dysfunction in children, including adrenal insufficiency, and found a markedly higher incidence of multiple neurohormonal dysfunctions in children with sepsis (249). These findings suggest both that neuroendocrine deficiency is common in pediatric sepsis and that many neurohormonal responses may be affected (249). Generally, adrenal insufficiency in the case of catecholamine-resistant shock is assumed at a random total cortisol level of <18 μg/dL (496 nmol/L). Dose recommendations for treatment of shock are 50 mg/kg, followed by the same dose as a 24-hr infusion (248, 251). Although not responsible for ordering steroids, it is essential that nurses work collaboratively to recognize the presence of refractory shock and initiate both timely measurement of cortisol levels and administration of hydrocortisone therapy when appropriate.
1. We suggest that critically ill pediatric patients receive goal-directed therapy for sedation and analgesia (grade 2D).
Pain causes energy expenditure and increases oxygen demand. Nurses play a key role in addressing this issue. Sedation and analgesia are commonly used in pediatric patients with severe sepsis to relieve pain, support mechanical ventilation, and reduce oxygen demand (252). The first step to initiating sedation and analgesia is to rule out physiologic causes of agitation, including hypoxemia, pain, hypercapnea, and cerebral hypoperfusion. Addressing the child's comfort by providing analgesia and sedation and decreasing restlessness helps to preserve oxygen for use by major organs (253). There are no data supporting any specific medications; therefore, drugs and dosages are based on the child's response. Therapy should be goal-directed using a validated scale to determine the child's level of comfort (254). In addition, comfort measures including appropriate positioning, gentle touch, and managing the environment to decrease or eliminate noxious stimuli are essential.
E. Therapeutic End Points
1. We recommend the use of therapeutic end points to guide interventions for the pediatric patient with severe sepsis and septic shock (grade 1D).
Therapeutic end points have been established for both initial resuscitation and ongoing treatment. The goals for the first hour of resuscitation remain focused on airway, breathing, and circulation. The therapeutic end points include a capillary refill time <2 secs, normal pulses, no differential between peripheral and central pulses, warm extremities, urine output >1 mL/kg/hr, normal mental status and normal glucose, ionized calcium, and blood pressure for age (247).
Once the initial resuscitation has taken place, attention is required to verify the effects of hypovolemia and cardiac and vascular dysfunction. The goals of stabilization are: normal perfusion; a perfusion pressure normal for age; superior vena cava or mixed venous oxygen saturation of >70%; and cardiac index >3.3 L/min/m2 and <6.0 L/min/m2 (255). The therapeutic end points are a capillary refill time <2 secs, normal pulses with no difference between peripheral and central pulses, warm extremities, urine output >1 mL/kg/hr, normal mental status, cardiac index >3.3 L/min/m2 and <6.0 L/min/m2, and superior vena cava or mixed venous oxygen saturation >70%. Cardiac index is augmented by increasing preload (247). Monitoring includes heart rate, oxygen saturation, blood pressure, temperature, urine output, central venous pressure, pulmonary artery pressure, cardiac output, glucose, and calcium (247).
This document provides a summary of the evidence that currently exists to underpin the nursing care of the patient with severe sepsis. Several limitations relate to the document, including the time and resources available to develop these recommendations and the lack of evidence that exists in many areas of care. Whereas a concerted effort was made to summarize the evidence from existing research and guidelines and reach consensus as to the level of support for nursing care considerations, much of the work was undertaken by small groups of two to three authors, with discussion and consensus by the entire author group then achieved through e-mail discussion. Although this provided an opportunity for all authors to raise concerns regarding grading of recommendations, the depth of discussion was confined to that possible by e-mail.
As outlined, multiple areas of nursing care have either no evidence to inform practice or the level of evidence is confined to expert opinion. Research to identify the most appropriate nursing interventions for severe sepsis patients is urgently required. Areas that are particularly needed include recognition of deterioration and diagnosis of sepsis, type and effect of early resuscitative measures, effective methods of hemodynamic assessment and support, type and effect of supportive care such as nutrition therapy, pressure ulcer prevention and management, mouth and eye care, and application of these interventions to the pediatric patient with severe sepsis. Identification of new evidence should inform the ongoing care of the severely septic patient and, as such, this document represents an ongoing process.
We acknowledge and appreciate the input of R. Phillip Dellinger, MD, during the inception of this project, particularly as it related to his experience with the development of the Surviving Sepsis Campaign Guidelines for the Management of Severe Sepsis and Septic Shock. We thank Gordon Speed for his review of the document in relation to comprehensiveness, logical flow, and use of terminology.
1.Angus DC, Linde-Zwirble WT, Lidicker J, et al: Epidemiology of severe sepsis in the United States: Analysis of incidence, outcome, and associated costs of care. Crit Care Med 2001; 29:1303–1310
2.ARISE, ANZICS APD Management Committee: The outcome of patients with sepsis and septic shock presenting to emergency departments in Australia and New Zealand. Crit Care Resusc 2007; 9:8–18
3.Dellinger RP, Carlet JM, Masur H, et al: Surviving Sepsis Campaign guidelines for management of severe sepsis and septic shock. Crit Care Med 2004; 32:858–873
4.Dellinger RP, Levy MM, Carlet JM, et al: Surviving Sepsis Campaign: International guidelines for management of severe sepsis and septic shock: 2008. Crit Care Med 2008; 36:296–327
5.Guyatt G, Gutterman D, Baumann MH, et al: Grading strength of recommendations and quality of evidence in clinical guidelines: Report from an American College of Chest Physicians task force. Chest 2006; 129:174–181
6.Prior M, Guerin M, Grimmer-Somers K: The effectiveness of clinical guideline implementation strategies—A synthesis of systematic review findings. J Eval Clin Pract 2008; 14:888–897
7.Safdar N, Abad C: Educational interventions for prevention of healthcare-associated infection: A systematic review. Crit Care Med 2008; 36:933–940
8.Eggimann P, Pittet D: Infection control in the ICU. Chest 2001; 120:2059–2093
9.Jarvis WR: The Lowbury Lecture. The United States approach to strategies in the battle against healthcare-associated infections, 2006: Transitioning from benchmarking to zero tolerance and clinician accountability. J Hosp Infect 2007; 65:3–9
10.Yokoe DS, Mermel LA, Anderson DJ, et al: A compendium of strategies to prevent healthcare-associated infections in acute care hospitals. Infect Control Hosp Epidemiol 2008; 29:S12–S21
11.Harbarth S, Sax H, Gastmeier P: The preventable proportion of nosocomial infections: An overview of published reports J Hosp Infect 2003; 54:258–266
12.Berenholtz SM, Pronovost PJ, Lipsett PA, et al: Eliminating catheter-related bloodstream infections in the intensive care unit. Crit Care Med 2004; 32:2014–2020
13.Pronovost P, Needham D, Berenholtz S, et al: An intervention to decrease catheter-related bloodstream infections in the ICU. N Engl J Med 2006; 355:2725–2732
14.Condon RE, Schulte WJ, Malangoni MA, et al: Effectiveness of a surgical wound surveillance program. Arch Surg 1983; 118:303–307
15.Cruse P: Wound infection surveillance. Rev Infect Dis 1981; 4:734–737
16.Cruse PJ, Foord R: The epidemiology of wound infection: A 10-year prospective study of 62,939 wounds. Surg Clin North Am 1980; 60:27–40
17.Gastmeier P, Geffers C: Prevention of catheter-related bloodstream infections: Analysis of studies published between 2002 and 2005. J Hosp Infect 2006; 64:326–335
18.Haley RW, Culver DH, White JW, et al: The efficacy of infection surveillance and control programs in preventing nosocomial infections in US hospitals. Am J Epidemiol 1985; 121:182–205
19.Sykes PK, Brodribb RK, McLaws ML, et al: When continuous surgical site infection surveillance is interrupted: The Royal Hobart Hospital experience. Am J Infect Control 2005; 33:422–427
20.Boyce JM, Pittet D, Healthcare Infection Control Practices Advisor Committee: Guideline for hand hygiene in health-care settings: Recommendations of the Healthcare Infection Control Practices Advisory Committee and the HIPAC/SHEA/APIC/IDSA Hand Hygiene Task Force. Am J Infect Control 2002; 30:S1–S46
21.Pratt RJ, Pellowe CM, Wilson JA, et al: EPIC2: National evidence-based guidelines for preventing healthcare-associated infections in NHS hospitals in England. J Hosp Infect 2007; 65:S1–S64
22.Clark L, Smith W, Young L: Protective clothing: Principles and guidance. London, UK, Infection Control Nurses Association, 2002
23.Corona A, Raimondi F: Prevention of nosocomial infection in the ICU setting. Minerva Anestesiologica 2004; 70:329–337
24.Safdar N, Dezfulian C, Collard HR, et al: Clinical and economic consequences of ventilator-associated pneumonia: A systematic review. Crit Care Med 2005; 33:2184–2193
25.Cook DJ, Walter SD, Cook RJ, et al: Incidence of and risk factors for ventilator-associated pneumonia in critically ill patients. Ann Intern Med 1998; 129:433–440
26.Tejerina E, Frutos-Vivar F, Restrepo MI, et al: Incidence, risk factors, and outcome of ventilator-associated pneumonia. J Crit Care 2006; 21:56–65
27.Warren DK, Shukla SJ, Olsen MA, et al: Outcome and attributable cost of ventilator-associated pneumonia among intensive care unit patients in a suburban medical center. Crit Care Med 2003; 31:1312–1317
28.Lai K, Baker S, Fontecchio S: Impact of a program of intensive surveillance and interventions targeting ventilated patients in the reduction of ventilator-associated pneumonia and its cost-effectiveness. Infect Control Hosp Epidemiol 2003; 24:859–863
29.Zack JE, Garrison T, Trovillion E, et al: Effect of an education program aimed at reducing the occurrence of ventilator-associated pneumonia. Crit Care Med 2002; 30:2407–2412
30.Lorente L, Blot S, Rello J: Evidence on measures for the prevention of ventilator-associated pneumonia. Eur Respir J 2007; 30:1193–1207
31.Wip C, Napolitano L: Bundles to prevent ventilator-associated pneumonia: how valuable are they? Curr Opin Infect Dis 2009; 22:159–166
32.Muscedere J, Dodek P, Keenan S, et al: Comprehensive evidence-based clinical practice guidelines for ventilator-associated pneumonia: Diagnosis and treatment. J Crit Care 2008; 23:138–147
33.Huxley EJ, Viroslav J, Gray WR, et al: Pharyngeal aspiration in normal adults and patients with depressed consciousness. Am J Med 1978; 64:564–568
34.Ibáñez J, Peñafiel A, Raurich JM, et al: Gastroesophageal reflux in intubated patients receiving enteral nutrition: Effect of supine and semirecumbent positions. JPEN J Parenter Enteral Nutr 1992; 16:419–422
35.Orozco-Levi M, Torres A, Ferrer M, et al: Seminirecumbent position protects from pulmonary aspiration but not completely from gastroesophageal reflux in mechanically ventilated patients. Am J Respir Crit Care Med 1995; 152:1387–1390
36.Torres A, Serra-Batlles J, Ros E, et al: Pulmonary aspiration of gastric contents in patients receiving mechanical ventilation: the effect of body position. Ann Intern Med 1992; 116:540–543
37.Drakulovic MB, Torres A, Bauer TT, et al: Supine body position as a risk factor for nosocomial pneumonia in mechanically ventilated patients: A randomised trial. Lancet 1999; 354:1851–1858
38.Fernández-Crehuet R, Díaz-Molina C, de Irala J, et al: Nosocomial infection in an intensive-care unit: Identification of risk factors. Infect Control Hosp Epidemiol 1997; 18:825–830
39.Kollef MH: Ventilator-associated pneumonia. A multivariate analysis. JAMA 1993; 270:1965–1970
40.Song HJ, Liu JT, Gao SQ, et al: Clinical investigation on the compliance and the validity of ventilator bundle. Zhongguo Wei Zhong Bing Ji Jiu Yi Xue 2009; 21:660–663
41.van Nieuwenhoven CA, Vandenbroucke-Grauls C, van Tiel FH, et al: Feasibility and effects of the semirecumbent position to prevent ventilator-associated pneumonia: A randomized study. Crit Care Med 2006; 34:396–402
42.Cason CL, Tyner T, Saunders S, et al: Nurses' implementation of guidelines for ventilator-associated pneumonia from the Centers for Disease Control and Prevention. Am J Crit Care 2007; 16:28–36
43.Dezfulian C, Shojania K, Collard HR, et al: Subglottic secretion drainage for preventing ventilator-associated pneumonia: A meta-analysis. Am J Med 2005; 118:11–18
44.Kollef MH, Afessa B, Anzueto A, et al: Silver-coated endotracheal tubes and incidence of ventilator-associated pneumonia: The NASCENT randomized trial. JAMA 2008; 300:805–813
45.Rello J, Kollef M, Diaz E, et al: Reduced burden of bacterial airway colonization with a novel silver-coated endotracheal tube in a randomized multiple-center feasibility study. Crit Care Med 2006; 34:2766–2772
46.Poelaert J, Depuydt P, De Wolf A, et al: Polyurethane cuffed endotracheal tubes to prevent early postoperative pneumonia after cardiac surgery: A pilot study. J Thoracic Cardiovasc Surg 2008; 135:771–776
47.Rello J, Soñora R, Jubert P, et al: Pneumonia in intubated patients: Role of respiratory airway care. Am J Respir Crit Care Med 1996; 154:111–115
48.Niël-Weise BS, Wille JC, van den Broek PJ: Humidification policies for mechanically ventilated intensive care patients and prevention of ventilator-associated pneumonia: A systematic review of randomized controlled trials. J Hosp Infect 2007; 65:285–291
49.Davis K Jr, Evans SL, Campbell RS, et al: Prolonged use of heat and moisture exchangers does not affect device efficiency or frequency rate of nosocomial pneumonia. Crit Care Med 2000; 28:1412–1418
50.Thomachot L, Leone M, Razzouk K, et al: Randomized clinical trial of extended use of a hydrophobic condenser humidifier: 1 vs. 7 days. Crit Care Med 2002; 30:232–237
51.Tsai TP, Lin YT, Wang YC, et al: Ventilator-associated pneumonia and frequency of circuit changes. Chest 2004; 126:898S
52.Thomson L, Morton R, Cuthbertson S, et al: Tracheal suctioning of adults with an artificial airway. Best Practice 2000; 4:1–6
53.Celik SS, Elbas NO: The standard of suction for patients undergoing endotracheal intubation. Intensive Crit Care Nurs 2000; 16:191–198
54.Day KM, Haub N, Betts H, et al: Hyperglycemia is associated with morbidity in critically ill children with meningococcal sepsis. Pediatr Crit Care Med 2008; 9:636–640
55.Rolls K, Smith K, Jones P, et al: Suctioning an adult with a tracheal tube. NSW Health Statewide Guidelines for Intensive Care. New South Wales Health, Sydney, 2007
56.Wood CJ: Endotracheal suctioning: A literature review. Intensive Crit Care Nurs 1998; 14:124–136
57.Pedersen CM, Rosendahl-Nielsen M, Hjermind J, et al: Endotracheal suctioning of the adult intubated patient—What is the evidence? Intensive Crit Care Nurs 2009; 25:21–30
58.Craven DE, Driks MR: Nosocomial pneumonia in the intubated patient. Semin Respir Infect 1987; 2:20–33
59.Torres A, el-Ebiary M, González J, et al: Gastric and pharyngeal flora in nosocomial pneumonia acquired during mechanical ventilation. Am Rev Respir Dis 1993; 148:352–357
60.Vallés J, Artigas A, Rello J, et al: Continuous aspiration of subglottic secretions in preventing ventilator-associated pneumonia. Ann Intern Med 1995; 122:179–186
61.Abele-Horn M, Dauber A, Bauernfeind A, et al: Decrease in nosocomial pneumonia in ventilated patients by selective oropharyngeal decontamination (SOD). Intensive Care Med 1997; 23:187–195
62.Johanson WG Jr, Seidenfeld JJ, de los Santos R, et al: Prevention of nosocomial pneumonia using topical and parenteral antimicrobial agents. Am Rev Respir Dis 1988; 137:265–272
63.Berry A, Davidson P: Consensus-based clinical guideline for the provision of oral care for the critically ill adult. NSW Health Statewide Guidelines for Intensive Care. New South Wales Health, Sydney, 2007
64.Fields LB: Oral care intervention to reduce incidence of ventilator-associated pneumonia in the neurologic intensive care unit. J Neurosci Nurs 2008; 40:291–298
65.Garcia R, Jendresky L, Colbert L, et al: Reducing ventilator-associated pneumonia through advanced oral-dental care: A 48-month study. Am J Crit Care 2009; 18:523–532
66.Munro CL, Grap MJ, Jones DJ, et al: Chlorhexidine, toothbrushing, and preventing ventilator-associated pneumonia in critically ill adults. Am J Crit Care 2009; 18:428–437
67.Weireter L, Collins J, et al: Impact of a monitored program of care on incidence of ventilator-associated pneumonia: results of a longterm performance-improvement project. J Am Coll Surg 2009; 208:700–704; discussion 704–705
68.Ross A, Crumpler J: The impact of an evidence-based practice education program on the role of oral care in the prevention of ventilator-associated pneumonia. Intensive Crit Care Nurs 2007; 23:132–136
69.Blot S, Vandijck D, Labeau S: Oral care of intubated patients. Clin Pulmonary Med 2008; 15:153–160
70.Grap MJ, Munro CL, Ashtiani B, et al: Oral care interventions in critical care: Frequency and documentation. Am J Crit Care 2003; 12:113–118
71.Jones DJ, Munro CL: Oral care and the risk of bloodstream infections in mechanically ventilated adults: A review. Intensive Crit Care Nurs 2008; 24:152–161
72.Munro CL, Grap MJ: Oral health and care in the intensive care unit: State of the science. Am J Crit Care 2004; 13:25–33
73.Choo A, Delac DM, Messer LB: Oral hygiene measures and promotion: Review and considerations. Aust Dent J 2001; 46:166–173
74.Moshrefi A: Chlorhexidine. J West Soc Periodontol Periodontal Abstr 2002; 50:5–9
75.Fourrier F, Cau-Pottier E, Boutigny H, et al: Effects of dental plaque antiseptic decontamination on bacterial colonization and nosocomial infections in critically ill patients. Intensive Care Med 2000; 26:1239–1247
76.DeRiso AJ, Ladowski JS, Dillon TA, et al: Chlorhexidine gluconate 0.12% oral rinse reduces the incidence of total nosocomial respiratory infection and nonprophylactic systemic antibiotic use in patients undergoing heart surgery. Chest 1996; 109:1556–1561
77.Chan EY, Ruest A, Meade MO, et al: Oral decontamination for prevention of pneumonia in mechanically ventilated adults: Systematic review and meta-analysis. BMJ 2007; 334:889–893
78.Chlebicki MP, Safdar N: Topical chlorhexidine for prevention of ventilator-associated pneumonia: A meta-analysis. Crit Care Med 2007; 35:595–602
79.Tantipong H, Morkchareonpong C, Jaiyindee S, et al: Randomized controlled trial and meta-analysis of oral decontamination with 2% chlorhexidine solution for the prevention of ventilator-associated pneumonia. Infect Control Hosp Epidemiol 2008; 29:131–136
80.Abidia RF: Oral care in the intensive care unit: A review. J Contemp Dent Pract 2007; 8:76–82
81.Rello J, Koulenti D, Blot S, et al: Oral care practices in intensive care units: A survey of 59 European ICUs. Intensive Care Med 2007; 33:1066–1070
82.Galpern D, Guerrero A, Tu A, et al: Effectiveness of a central line bundle campaign on line-associated infections in the intensive care unit. Surgery 2008; 144:492–495
83.Tsuchida T, Makimoto K, Toki M, et al: The effectiveness of a nurse-initiated intervention to reduce catheter-associated bloodstream infections in an urban acute hospital: An intervention study with before and after comparison. Int J Nurs Stud 2007; 44:1324–1333
84.Carrer S, Bocchi A, Bortolotti M, et al: Effect of different sterile barrier precautions and central venous catheter dressing on the skin colonization around the insertion site. Minerva Anestesiologica 2005; 71:197–206
85.Hu KK, Lipsky BA, Veenstra DL, et al: Using maximal sterile barriers to prevent central venous catheter–related infection: A systematic evidence-based review. Am J Infect Control 2004; 32:142–146
86.Marschall J, Mermel LA, Classen D, et al: Strategies to prevent central line-associated bloodstream infections in acute care hospitals. Infect Control Hosp Epidemiol 2008; 29:S22–S30
87.Raad II, Hohn DC, Gilbreath BJ, et al: Prevention of central venous catheter-related infections by using maximal sterile barrier precautions during insertion. Infect Control Hosp Epidemiol 1994; 15:231–238
88.Young EM, Commiskey ML, Wilson SJ: Translating evidence into practice to prevent central venous catheterassociated bloodstream infections: A systems-based intervention. Am J Infect Control 2006; 34:503–506
89.Maki DG: Yes, Virginia, aseptic technique is very important: Maximal barrier precautions during insertion reduce the risk of central venous catheter-related bacteremia. Infect Control Hosp Epidemiol 1994; 15:227–230
90.Mermel LA, McCormick RD, Springman SR, et al: The pathogenesis and epidemiology of catheter-related infection with pulmonary artery Swan-Ganz catheters: A prospective study utilizing molecular subtyping. Am J Med 1991; 91:197S–205S
91.Mimoz O, Pieroni L, Lawrence C, et al: Prospective, randomized trial of two antiseptic solutions for prevention of central venous or arterial catheter colonization and infection in intensive care unit patients. Crit Care Med 1996; 24:1818–1823
92.Small H, Adams D, Casey AL, et al: Efficacy of adding 2% (w/v) chlorhexidine gluconate to 70% (v/v) isopropyl alcohol for skin disinfection prior to peripheral venous cannulation. Infect Control Hosp Epidemiol 2008; 29:963–965
93.Vallés J, Fernández I, Alcaraz D, et al: Prospective randomized trial of 3 antiseptic solutions for prevention of catheter colonization in an intensive care unit for adult patients. Infect Control Hosp Epidemiol 2008; 29:847–853
94.Gillies D, O'Riordan L, Wallen M, et al: Optimal timing for intravenous administration set replacement. Cochrane Database System Rev 2005; 4:CD003588
95.Avila-Figueroa C, Goldmann DA, Richardson DK, et al: Intravenous lipid emulsions are the major determinant of coagulase-negative staphylococcal bacteremia in very low birth weight newborns. Pediatr Infect Dis J 1998; 17:10–17
96.Crocker KS, Noga R, Filibeck DJ, et al: Microbial growth comparisons of five commercial parenteral lipid emulsions. JPEN J Parenter Enteral Nutr 1984; 8:391–395
97.Hanna HA, Raad I: Blood products: A significant risk factor for long-term catheter-related bloodstream infections in cancer patients. Infect Control Hosp Epidemiol 2001; 22:165–166
98.Jarvis WR, Highsmith AK: Bacterial growth and endotoxin production in lipid emulsion. J Clin Microbiol 1984; 19:17–20
99.Raad I, Hanna HA, Awad A, et al: Optimal frequency of changing intravenous administration sets: is it safe to prolong use beyond 72 hours? Infect Control Hosp Epidemiol 2001; 22:136–139
100.Saiman L, Ludington E, Dawson JD, et al: Risk factors for Candida species colonization of neonatal intensive care unit patients. Pediatr Infect Dis J 2001; 20:1119–1124
101.Hanna H, Benjamin R, Chatzinikolaou I, et al: Long-term silicone central venous catheters impregnated with minocycline and rifampin decrease rates of catheter-related bloodstream infection in cancer patients: A prospective randomized clinical trial. J Clin Oncol 2004; 22:3163–3171
102.León C, Ruiz-Santana S, Rello J, et al: Benefits of minocycline and rifampin-impregnated central venous catheters. A prospective, randomized, double-blind, controlled, multicenter trial. Intensive Care Med 2004; 30:1891–1899
103.Raad I, Darouiche R, Dupuis J, et al: Central venous catheters coated with minocycline and rifampin for the prevention of catheter-related colonization and bloodstream infections. A randomized, double-blind trial. The Texas Medical Center Catheter Study Group. Ann Intern Med 1997; 127:267–274
104.Veenstra DL, Saint S, Saha S, et al: Efficacy of antiseptic-impregnated central venous catheters in preventing catheter-related bloodstream infection: A meta-analysis. JAMA 1999; 281:261–267
105.Darouiche RO, Raad II, Heard SO, et al: A comparison of two antimicrobial-impregnated central venous catheters. Catheter Study Group. N Engl J Med 1999; 340:1–8
106.Bratzler DW, Houck PM, Surgical Infection Prevention Guidelines Writers Workgoup: Antimicrobial prophylaxis for surgery: An advisory statement from the National Surgical Infection Prevention Project. Clin Infect Dis 2004; 38:1706–1715
107.Anderson DJ, Kaye KS, Classen D, et al: Strategies to prevent surgical site infections in acute care hospitals. Infect Control Hosp Epidemiol 2008; 29:S51–S61
108.Mangram AJ, Horan TC, Pearson ML, et al: Guideline for Prevention of Surgical Site Infection, 1999. Centers for Disease Control and Prevention (CDC) Hospital Infection Control Practices Advisory Committee. Am J Infect Control 1999; 27:97–132
109.Mishriki SF, Law DJ, Jeffery PJ: Factors affecting the incidence of postoperative wound infection. J Hosp Infect 1990; 16:223–230
110.Moro ML, Carrieri MP, Tozzi AE, et al: Risk factors for surgical wound infections in clean surgery: A multicenter study. Italian PRINOS Study Group. Ann Ital Chir 1996; 67:13–19
111.Winston KR: Hair and neurosurgery. Neurosurgy 1992; 31:320–329
112.Tanner J, Woodings D, Moncaster K: Preoperative hair removal to reduce surgical site infection. Cochrane Database System Rev 2006; 3:CD004122
113.Hamilton HW, Hamilton KR, Lone FJ: Preoperative hair removal. Can J Surg 1977; 20:269–271, 274
114.Seropian R, Reynolds BM: Wound infections after preoperative depilatory versus razor preparation. Am J Surg 1971; 121:251–254
115.Terranova A: The effects of diabetes mellitus on wound healing. Plastic Surgical Nursing 1991; 11:20–25
116.Zerr KJ, Furnary AP, Grunkemeier GL, et al: Glucose control lowers the risk of wound infection in diabetics after open heart operations. Ann Thorac Surg 1997; 63:356–361
117.Latham R, Lancaster AD, Covington JF, et al: The association of diabetes and glucose control with surgical-site infections among cardiothoracic surgery patients. Infect Control Hosp Epidemiol 2001; 22:607–612
118.Hunter JG, Padilla M, Cooper-Vastola S: Late clostridium perfringens breast implant infection after dental treatment. Ann Plastic Surg 1996; 36:309–312
119.Stuesse DC, Robinson JH, Durzinsky DS: A late sternal wound infection caused by hematogenous spread of bacteria. Chest 1995; 108:1742–1743
120.Velasco E, Thuler LC, Martins CA, et al: Risk factors for infectious complications after abdominal surgery for malignant disease. Am J Infect Control 1996; 24:1–6
121.Tenke P, Kovacs B, Bjerklund Johansen TE, et al: European and Asian guidelines on management and prevention of catheter-associated urinary tract infections. Int J Antimicrob Agents 2008; 31:S68–78
122.Wald HL, Ma A, Bratzler DW, et al: Indwelling urinary catheter use in the postoperative period: Analysis of the national surgical infection prevention project data. Arch Surg 2008; 143:551–557
123.Willson M, Wilde M, Webb ML, et al: Nursing interventions to reduce the risk of catheter-associated urinary tract infection: Part 2: Staff education, monitoring, and care techniques. J Wound Ostomy Continence Nurs 2009; 36:137–154
124.Garibaldi RA, Burke JP, Dickman ML, et al: Factors predisposing to bacteriuria during indwelling urethral catheterization. N Engl J Med 1974; 291:215–219
125.Gillespie WA, Lennon GG, Linton KB, et al: Prevention of urinary infection in gynaecology. BMJ 1964; 2:423–425
126.Kunin CM: Detection, prevention, and management of urinary tract infections. Third Editon. Philadelphia, PA, Lea and Febiger, 1979
128.Warren JW, Platt R, Thomas RJ, et al: Antibiotic irrigation and catheter-associated urinary-tract infections. N Engl J Med 1978; 299:570–573
130.Tsuchida T, Makimoto K, Ohsako S, et al: Relationship between catheter care and catheter-associated urinary tract infection at Japanese general hospitals: A prospective observational study. Int J Nurs Stud 2008; 45:352–361
131.Dieckhaus KD, Garibaldi RA: Prevention of catheter-associated urinary tract infections. In: Saunders infection control reference service. Abrutytn E, Goldmann DA, Scheckler WE (Eds). Philadelphia, PA, WB Saunders, 1998, pp 169–174
132.Ward V, Wilson J, Taylor L, et al: Preventing hospital-acquired infection: Clinical guidelines. London, UK, Public Health Laboratory Service, 1997
133.Garnacho-Montero J, Aldabó-Pallás T, Palomar-Martínez M, et al: Risk factors and prognosis of catheter-related bloodstream infection in critically ill patients: A multicenter study. Intensive Care Med 2008; 34:2185–2193
134.Pettigrew RA, Lang SD, Haydock DA, et al: Catheter-related sepsis in patients on intravenous nutrition: A prospective study of quantitative catheter cultures and guidewire changes for suspected sepsis. Br J Surg 1985; 72:52–55
135.Brundage JF: Interactions between influenza and bacterial respiratory pathogens: implications for pandemic preparedness. Lancet Infect Dis 2006; 6:303–312
136.Siegel JD, Rhinehart E, Jackson M, et al: 2007 Guideline for isolation precautions: preventing transmission of infectious agents in health care settings. Am J Infect Control 2007; 35:S65–S164
137.Levy MM, Fink MP, Marshall JC, et al: 2001 SCCM/ESICM/ACCP/ATS/SIS International Sepsis Definitions Conference. Crit Care Med 2003; 31:1250–1256
138.Kleinpell R: Implementing the Surviving Sepsis Campaign guidelines: Implications for nursing care. Advances in Sepsis 2005; 4:61–63
139.Clarke SP, Aiken LH: Failure to rescue: Needless deaths are prime examples of the need for more nurses at the bedside. Am J Nurs 2003; 103:42–47
140.Silber JH, Williams SV, Krakauer H, et al: Hospital and patient characteristics associated with death after surgery. A study of adverse occurrence and failure to rescue. Med Care 1992; 30:615–629
141.Ferrer R, Artigas A, Levy MM, et al: Improvement in process of care and outcome after a multicenter severe sepsis educational program in Spain. JAMA 2008; 299:2294–2303
142.Levy MM, Dellinger RP, Townsend SR, et al: The Surviving Sepsis Campaign: Results of an international guideline-based performance improvement program targeting severe sepsis. Crit Care Med 2010; 38:367–374
143.Kleinpell RM: The role of the critical care nurse in the assessment and management of the patient with severe sepsis. Crit Care Nurs Clin North Am 2003; 15:27–34
144.Robson WP, Daniels R: The Sepsis Six: helping patients to survive sepsis. Br J Nurs 2008; 17:16–21
147.Gao H, McDonnell A, Harrison DA, et al: Systematic review and evaluation of physiological track and trigger warning systems for identifying at-risk patients on the ward. Intensive Care Med 2007; 33:667–679
148.McGaughey J, Alderdice F, Fowler R, et al: Outreach and early warning systems (EWS) for the prevention of intensive care admission and death of critically ill adult patients on general hospital wards. Cochrane Database System Rev 2007; 3:CD005529
150.Moore LJ, Jones SL, Kreiner LA, et al: Validation of a screening tool for the early identification of sepsis. J Trauma 2009; 66:1539–1546
151.Reeves S, Lewin S: Interprofessional collaboration in the hospital: strategies and meanings. J Health Serv Res Policy 2004; 9:218–225
152.Haig KM, Sutton S, Whittington J: SBAR: A shared mental model for improving communication between clinicians. Jt Comm J Qual Patient Saf 2006; 32:167–175
153.Joint Commission Resources: The SBAR technique: Improves communication, enhances patient safety. Jt Comm Perspect Patient Saf 2005; 5:1–8
154.Featherstone P, Chalmers T, Smith GB: RSVP: A system for communication of deterioration in hospital patients. Br J Nurs 2008; 17:860–864
155.Andrews T, Waterman H: Packaging: A grounded theory of how to report physiological deterioration effectively. J Adv Nurs 2005; 52:473–481
156.DeVita MA, Smith GB, Adam SK, et al: “Identifying the hospitalised patient in crisis”—A consensus conference on the afferent limb of rapid response systems. Resuscitation 2010; 81:375–382
157.Sebat F (Ed): Designing, implementing, and enhancing a rapid response system. Chicago, IL, Society of Critical Care Medicine, 2009
158.Rivers E, Nguyen B, Havstad S, et al: Early goal-directed therapy in the treatment of severe sepsis and septic shock. N Engl J Med 2001; 345:1368–1377
160.Baldwin LN, Smith SA, Fender V, et al: An audit of compliance with the sepsis resuscitation care bundle in patients admitted to A&E with severe sepsis or septic shock. Int Emerg Nurs 2008; 16:250–256
161.Gao F, Melody T, Daniels DF, et al: The impact of compliance with 6-hour and 24-hour sepsis bundles on hospital mortality in patients with severe sepsis: A prospective observational study. Critical Care 2005; 9:R764–R770
162.McNeill G, Dixon M, Jenkins P: Can acute medicine units in the UK comply with the Surviving Sepsis Campaign's six-hour care bundle? Clin Med 2008; 8:163–165
163.Carlbom DJ, Rubenfeld GD: Barriers to implementing protocol-based sepsis resuscitation in the emergency department–results of a national survey. Crit Care Med 2007; 35:2525–2532
164.Nguyen HB, Lynch EL, Mou JA, et al: The utility of a quality improvement bundle in bridging the gap between research and standard care in the management of severe sepsis and septic shock in the emergency department. Acad Emerg Med 2007; 14:1079–1086
165.Trzeciak S, Dellinger RP, Abate NL, et al: Translating research to clinical practice: A 1-year experience with implementing early goal-directed therapy for septic shock in the emergency department. Chest 2006; 129:225–232
166.Mikkelsen ME, Miltiades AN, Gaieski DF, et al: Serum lactate is associated with mortality in severe sepsis independent of organ failure and shock. Crit Care Med 2009; 37:1670–1677
167.Amaravadi RK, Dimick JB, Pronovost PJ, et al: ICU nurse-to-patient ratio is associated with complications and resource use after esophagectomy. Intensive Care Med 2000; 26:1857–1862
168.Dimick JB, Swoboda SM, Pronovost PJ, et al: Effect of nurse-to-patient ratio in the intensive care unit on pulmonary complications and resource use after hepatectomy. Am J Crit Care 2001; 10:376–382
169.Kovner C, Gergen PJ: Nurse staffing levels and adverse events following surgery in U.S. hospitals. Image J Nurs Sch 1998; 30:315–321
170.Pronovost PJ, Jenckes MW, Dorman T, et al: Organizational characteristics of intensive care units related to outcomes of abdominal aortic surgery. JAMA 1999; 281:1310–1317
171.Unruh L: The effect of LPN reductions on RN patient load. J Nurs Adm 2003; 33:201–208
172.Giraud T, Dhainaut JF, Vaxelaire JF, et al: Iatrogenic complications in adult intensive care units: A prospective two-center study. Crit Care Med 1993; 21:40–51
173.Aiken LH, Clarke SP, Sloane DM, et al: Hospital nurse staffing and patient mortality, nurse burnout, and job dissatisfaction. JAMA 2002; 288:1987–1993
174.Clarke S, Donaldson N: Nurse staffing and patient care quality and safety. In: Patients and Quality–An Evidence-based Hand-book for Nurses. Hughes RG (Ed). Agency for Healthcare Research & Quality, Rockville, MD, 2008
175.Needleman J, Buerhaus P, Mattke S, et al: Nurse-staffing levels and the quality of care in hospitals. N Engl J Med 2002; 346:1715–1722
176.Fridkin SK, Pear SM, Williamson TH, et al: The role of understaffing in central venous catheter-associated bloodstream infections. Infect Control Hosp Epidemiol 1996; 17:150–158
177.Picard KM, O'Donoghue SC, Young-Kershaw DA, et al: Development and implementation of a multidisciplinary sepsis protocol. Crit Care Nurse 2006; 26:43–54
178.Sivayoham N: Management of severe sepsis and septic shock in the emergency department: A survey of current practice in emergency departments in England. Emerg Med J 2007; 24:422
180.O'Driscoll BR, Howard LS, Davison AG; British Thoracic Society: BTS guideline for emergency oxygen use in adult patients. Thorax 2008; 63 (Suppl 6):vi1–68
181.Resuscitation Council UK: Advanced life support. Fifth Edition. London, UK, Resuscitation Council UK, 2006
182.Robson W, Webster S, Blakemore K, et al: The use of a patient group direction to ensure prompt treatment of postoperative hypotension in orthopaedic patients. J Orthopaed Nursing 2003; 7:197–200
183.McKendry M, McGloin H, Saberi D, et al: Randomised controlled trial assessing the impact of a nurse delivered, flow monitored protocol for optimisation of circulatory status after cardiac surgery. BMJ 2004; 329:258
184.Phillips S: Legislative update. Twentieth anniversary. After 20 years, APNs are still standing together. Nurse Practitioner 2008; 33:10–34
186.Australian & New Zealand Society of Blood Transfusion, Royal College of Nursing Australia: Guidelines for the administration of blood components. 2004. Available at: http://www.anzsbt.org.au/publications/index.cfm
. Accessed December 28, 2009
188.Minton J, Clayton J, Sandoe J, et al: Improving early management of bloodstream infection: A quality improvement project. BMJ 2008; 336:440–443
189.Natsch S, Kullberg BJ, van der Meer JW, et al: Delay in administering the first dose of antibiotics in patients admitted to hospital with serious infections. Eur J Clin Microbiol Infect Dis 1998; 17:681–684
191.Thompson DS, Oberteuffer R, Dorman T: Sepsis alert and diagnostic system: integrating clinical systems to enhance study coordinator efficiency. Comput Inform Nurs 2003; 21:22–26; quiz 27–28
192.Boardman S, Richmond C, Robson W, et al: Prehospital management of a patient with severe sepsis. J Paramed Pract 2009; 1:183–188
193.Hollenberg SM, Ahrens TS, Annana D, et al: Practice parameters for hemodynamic support of sepsis in adult patients: 2004 update. Crit Care Med 2004; 32:1928–1948
194.Ahrens T: Hemodynamics in sepsis. AACN Adv Crit Care 2006; 17:435–445
195.Maxwell D, Carrigan L, Merritt C, et al: Comparison of continuous central venous oxygen saturation and standard central venous catheters in septic patients at a large, non-academic tertiary medical center. Crit Care Med 2009; 37:A216
196.Donati A, Romanelli M, Botticelli L, et al: Recombinant activated protein C treatment improves tissue perfusion and oxygenation in septic patients measured by near-infrared spectroscopy. Crit Care 2009; 13:S12
197.Leone M, Blidi S, Antonini F, et al: Oxygen tissue saturation is lower in nonsurvivors than in survivors after early resuscitation of septic shock. Anesthesiology 2009; 111:366–371
198.Doerschug KC, Delsing AS, Schmidt GA, et al: Impairments in microvascular reactivity are related to organ failure in human sepsis. Am J Physiol Heart Circ Physiol 2007; 293:H1065–H1071
199.Cohn SM, Nathens AB, Moore FA, et al: Tissue oxygenation saturation predicts the development of organ dysfunction during traumatic shock resuscitation. J Trauma 2007; 62:44–55
200.Bakker J, Jansen TC: Don't take vitals, take a lactate. Intensive Care Med 2007; 33:1863–1865
201.Howell MD, Donnino M, Clardy P, et al: Occult hypoperfusion and mortality in patients with suspected infection. Intensive Care Med 2007; 33:1892–1899
202.Micek ST, Roubinian N, Heuring T, et al: Before-after study of a standardized hospital order set for the management of septic shock. Crit Care Med 2006; 34:2707–2713
203.Shorr AF, Micek ST, Jackson WL Jr, et al: Economic implications of an evidence-based sepsis protocol: Can we improve outcomes and lower costs? Crit Care Med 2007; 35:1257–1262
204.Packman MI, Rackow EC: Optimum left heart filling pressure during fluid resuscitation of patients with hypovolemic and septic shock. Crit Care Med 1983; 11:165–169
205.Marik PE, Baram M, Vahid B: Does central venous pressure predict fluid responsiveness? A systematic review of the literature and the tale of seven mares. Chest 2008; 134:172–178
206.Chytra I, Pradl R, Bosman R, et al: Esophageal Doppler-guided fluid management decreases blood lactate levels in multiple-trauma patients: A randomized controlled trial. Crit Care 2007; 22:1–9
207.Conway D, Mayall R, Abdul-Latif M, et al: Randomized controlled trial investigating the influence of intravenous fluid titration using esophageal Doppler monitoring during bowel surgery. Anesthesia 2002; 57:845–849
208.Gan TJ, Soppitt A, Maroof M, et al: Goal-directed intraoperative fluid administration reduces length of hospital stay after major surgery. Anesthesiology 2002; 97:820–826
209.Mythen MG, Webb AR: Perioperative plasma volume expansion reduces the incidence of gut mucosal hypoperfusion during cardiac surgery. Arch Surg 1995; 130:423–429
211.Sinclair S, James S, Singer M: Intraoperative intravascular volume optimization and length of hospital stay after repair of proximal femoral fracture: Randomized controlled trial. BMJ 1997; 315:909–912
212.Venn R, Steele A, Richardson P, et al: Randomized controlled trial to investigate influence of the fluid challenge on duration of hospital stay and perioperative morbidity in patients with hip fractures. Br J Anaesth 2002; 88:65–71
213.Wakeling HG, McFall MR, Jenkins CS, et al: Intraoperative oesophageal Doppler guided fluid management shortens postoperative hospital stay after major bowel surgery. Br J Anaesth 2005; 95:634–642
214.Eachempati S, Young C, Alexander J, et al: The clinical use of an esophageal Doppler monitor for hemodynamic monitoring in sepsis. J Clin Monit Comput 1999; 15:223–225
215.Marx G, Cope T, McCrossan L, et al: Assessing fluid responsiveness by stroke volume variation in mechanically ventilated patients with severe sepsis. Eur J Anaesthesiol 2004; 21:132–138
216.Santolucito J: The role of peripherally inserted central catheters in the treatment of the critically-ill. J Assoc Vasc Access 2007; 12:208–217
217.Heyland D, Dhaliwal R, Drover J, et al: Canadian clinical practice guidelines for nutrition support in mechanically ventilated, critically ill adult patients. J Parenter Enteral Nutr 2003; 27:355–373
218.Giner M, Laviano A, Meguid MM, et al: In 1995 a correlation between malnutrition and poor outcome in critically ill patients still exists. Nutrition 1996; 12:23–29
219.Martindale RG, McClave SA, Vanek VW, et al: Guidelines for the provision and assessment of nutrition support therapy in the adult critically ill patient: Society of Critical Care Medicine and American Society for Parenteral and Enteral Nutrition: Executive Summary. Crit Care Med 2009; 37:1757–1761
222.Kreymann KG, Berger MM, Deutz NE, et al: ESPEN Guidelines on Enteral Nutrition: Intensive care. Clin Nutrition 2006; 25:210–223
223.Jones NE, Dhaliwal R, Day AG, et al: Factors predicting adherence to the Canadian Clinical Practice Guidelines for nutrition support in mechanically ventilated, critically ill adult patients. J Crit Care 2008; 23:301–307
224.Gramlich L, Kichian K, Pinilla J, et al: Does enteral nutrition compared to parenteral nutrition result in better outcomes in critically ill adult patients? A systematic review of the literature. Nutrition 2004; 20:843–848
225.Simpson F, Doig GS: Parenteral vs. enteral nutrition in the critically ill patient: A meta-analysis of trials using the intention to treat principle. Intensive Care Med 2005; 31:12–23
226.Marik PE, Zaloga GP: Early enteral nutrition in acutely ill patients: A systematic review. Crit Care Med 2001; 29:2264–2270
227.Koroloff N, Boots R, Lipman J, et al: A randomised controlled study of the efficacy of hypromellose and Lacri-Lube combination versus polyethylene/cling wrap to prevent corneal epithelial breakdown in the semiconscious intensive care patient. Intensive Care Med 2004; 30:1122–1126
228.Hernandez EV, Mannis MJ: Superficial keratopathy in intensive care unit patients. Am J Ophthalmol 1997; 124:212–216
229.Imanaka H, Taenaka N, Nakamura J, et al: Ocular surface disorders in the critically ill. Anesth Analg 1997; 85:343–346
230.Lenart SB, Garrity JA: Eye care for patients receiving neuromuscular blocking agents or propofol during mechanical ventilation. Am J Crit Care 2000; 9:188–191
231.Marshall A, Elliott R, Rolls K, et al: Eyecare in the critically ill: Clinical practice guideline. Aust Crit Care 2008; 2:97–109
232.Bates J, Dwyer R, O'Toole L, et al: Corneal protection in critically ill patients: A randomized controlled trial of three methods. Clinical Intensive Care 2004; 15:23–26
233.European Pressure Ulcer Advisory Panel (EPUAP), National Pressure Ulcer Advisory Panel (NPUAP). Pressure ulcer prevention: Quick reference guide2009a: Available at: http://www.epuap.org/guidelines.html
. Accessed December 5, 2009
234.European Pressure Ulcer Advisory Panel (EPUAP), National Pressure Ulcer Advisory Panel (NPUAP): Pressure ulcer treatment: Quick reference guide2009b: Available at: http://www.epuap.org/guidelines.html
. Accessed December 5, 2009
235.Elliott R, McKinley S, Fox V: Quality improvement program to reduce the prevalence of pressure ulcers in an intensive care unit. Am J Crit Care 2008; 17:328–334
236.de Laat EH, Schoonhoven L, Pickkers P, et al: Epidemiology, risk and prevention of pressure ulcers in critically ill patients: A literature review. J Wound Care 2006; 15:269–275
237.Boyle M, Green M: Pressure sores in intensive care: defining their incidence and associated factors and assessing the utility of two pressure sore risk assessment tools. Aust Crit Care 2001; 14:24–30
238.Fife C, Otto G, Capsuto EG, et al: Incidence of pressure ulcers in a neurologic intensive care unit. Crit Care Med 2001; 29:283–290
239.Seongsook J, Ihnsook J, Younghee L: Validity of pressure ulcer risk assessment scales; Cubbin and Jackson, Braden, and Douglas scale. Int J Nurs Stud 2004; 41:199–204
240.Kottner J, Raeder K, Halfens R, et al: A systematic review of interrater reliability of pressure ulcer classification systems. J Clin Nurs 2009; 18:315–336
241.Stausberg J, Kiefer E: Classification of pressure ulcers: A systematic literature review. Stud Health Technol Inform 2009; 146:511–515
242.Hopkins RO, Spuhler VJ, Thomsen GE: Transforming ICU culture to facilitate early mobility. Crit Care Clin 2007; 23:81–96
243.Watson RS, Carcillo JA: Scope and epidemiology of pediatric sepsis. Pediatr Crit Care Med 2005; 6:S3–S5
244.Watson RS, Carcillo JA, Linde-Zwirble WT, et al: The epidemiology of severe sepsis in children in the United States. Am J Respir Crit Care Med 2003; 167:695–701
245.von Rosenstiel N, von Rosenstiel I, Adam D: Management of sepsis and septic shock in infants and children. Paediatr Drugs 2001; 3:9–27
246.Goldstein B, Giroir B, Randolph A, et al: International pediatric sepsis consensus conference: definitions for sepsis and organ dysfunction in pediatrics. Pediatr Crit Care Med 2005; 6:2–8
247.Brierley J, Carcillo JA, Choong K, et al: Clinical practice parameters for hemodynamic support of pediatric and neonatal septic shock: 2007 update from the American College of Critical Care Medicine. Crit Care Med 2009; 37:666–688
248.Parker MM, Hazelzet JA, Carcillo JA: Pediatric considerations. Crit Care Med 2004; 32:S591–S594
249.Aneja R, Carcillo JA: What is the rationale for hydrocortisone treatment in children with infection-related adrenal insufficiency and septic shock? Arch Dis Child 2007; 92:165–169
250.Dichter C, Curley M: Shock. In: Critical care nursing of infants and children. Second Edition. Curley M, Moloney-Harmon P (Eds). Philadelphia, PA: WB Saunders, 2001, pp 937
251.Hebbar K, Rigby MR, Felner EI, et al: Neuroendocrine dysfunction in pediatric critical illness. Pediatr Crit Care Med 2009; 10:35–40
252.Sorce L: Adverse responses: Sedation, analgesia and neuromuscular blocking agents in critically ill children. Crit Care Nurs Clin North Am 2005; 17:441–450, xi-xii
253.Moloney-Harmon P: Pediatric sepsis: The infection unto death. Crit Care Nurs Clin North Am 2005; 17:417–429, xi
254.Curley MA, Harris SK, Fraser KA, et al: State Behavioral Scale: A sedation assessment instrument for infants and young children supported on mechanical ventilation. Pediatr Crit Care Med 2006; 7:107–114
255.Barton P, Kalil AC, Nadel S, et al: Safety, pharmacokinetics, and pharmacodynamics of drotrecogin alfa (activated) in children with severe sepsis. Pediatrics 2004; 113:7–17
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