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Anesthesiology:
doi: 10.1097/ALN.0b013e318215d65a
Education: Anesthesia Literature Review

Anesthesia Literature Review

Section Editor(s): Brennan, Timothy J. Ph.D., M.D., Editor

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Perioperative Medicine

J. Lance Lichtor, M.D., and Joseph F. Antognini, M.D., Editors
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Prehospital intravenous fluid administration is associated with higher mortality in trauma patients: A national trauma bank data analysis. Ann Surg 2011; 253:271–7

Despite the high prevalence of use, IV fluid administration may not improve survival in trauma patients and may, in fact, result in increased complications. Therefore, a large retrospective analysis was conducted using the National Trauma Data Bank to analyze the risk of mortality in trauma patients who received versus those who did not receive prehospital IV fluids. Records were collected during a 5-yr period from 776,734 patients. Of the patients, 311,071 (49%) received prehospital IV fluids.
Overall mortality was 4.6%. Patients were more likely to receive an IV line if they had a penetrating trauma. Mortality was significantly higher in patients who received prehospital IV fluids compared with those who did not receive fluids (4.8% vs. 4.5%; P < 0.001). Multivariable regression analysis demonstrated that patients who received fluids were more likely to die than those who did not receive fluids, regardless of the cause of trauma (see fig. below).
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Interpretation
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There is increasing evidence to show that limiting IV fluid administration may improve outcome in trauma patients. In this study of traumatic injury patients included in the National Trauma Data Bank, prehospital IV line placement and/or fluid resuscitation was associated with slightly greater mortality overall and in multiple patient subgroups analyzed.
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Endovascular repair of blunt traumatic thoracic aortic injuries: Seven-year single-center experience. Arch Surg 2010; 145:679–83

Open repair of blunt thoracic aortic injury is the standard of care; yet, it is associated with significant mortality rates (5–28%) and has significant complications. Thoracic endovascular aortic repair using stent grafts is an alternative method that may provide improved patient outcomes. This retrospective single-center study examined the short- and mid-term outcomes of thoracic endovascular aortic repair in 24 patients during a 7-yr period. The repair was performed within 24 h in 75% of patients. The procedure was successful in all patients. One patient died within 30 days; thus, initial mortality was low. Another patient died 2 yr after the initial trauma, for reasons unrelated to the trauma. One patient died within 30 days because of multisystem organ failure. Intraoperative systemic heparin was required in only 16% of patients, and vascular access site complications occurred in 8% of patients; one patient required a secondary intervention 1 day after treatment. After 21 months, there have been no delayed device failures or complications.
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Interpretation
In this single-institution study of 24 patients with blunt thoracic aortic injury, percutaneous commercially available stent grafts were inserted. Early mortality was only 4%. Long-term follow-up is needed to determine later outcomes with these grafts.
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Apixaban versus enoxaparin for thromboprophylaxis after hip replacement. N Engl J Med 2010; 363:2487–98

Despite the standard use of prophylaxis in patients undergoing hip replacement, thrombotic events still occur in up to 20% of patients. This phase 3 randomized, double-blind, double-dummy trial was conducted to compare the effects of apixaban with enoxaparin in patients undergoing elective total hip replacement. Patients received either apixaban, 2.5 mg, orally twice daily beginning 12–24 h after surgical closure (n = 1,949) or enoxaparin, 40 mg, subcutaneously every 24 h beginning 12 h before surgery (n = 1,917). Both drugs were continued for 35 days after surgery.
Patients in the apixaban group demonstrated superior outcomes compared with patients in the enoxaparin group (see fig. near top of next page). The primary outcome (asymptomatic or symptomatic deep-vein thrombosis, nonfatal pulmonary embolism, or death from any cause) favored apixaban. Based on a composite outcome, apixaban did not increase the risk of major bleeding and clinically relevant nonmajor bleeding.
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Interpretation
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Thromboprophylaxis techniques require injections after surgery that must continue even after patients are discharged to home. Apixaban, an orally available highly specific factor Xa inhibitor, when continued for 35 days after surgery, was more effective than standard therapy, enoxaparin injection. Specifically, the risk of major venous thromboembolism was reduced without an increased bleeding risk.
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Immediate interpersonal and intermanual referral of sensations following anesthetic block of one arm. Arch Neurol 2010; 67:1521–3

Cortical reorganization can result in phenomena, such as sensory mirror neuron phenomena (i.e., sensing touch when another individual is touched) and sensory referral (i.e., sensations felt bilaterally in response to a single ipsilateral stimulus). This six-patient case series investigated whether interpersonal and intermanual sensory referral occurs after brachial plexus block of a single limb in patients undergoing orthopedic surgery. Tests were performed 30 min after surgery in awake patients.
When a volunteer positioned his or her own hand next to the blocked or intact arm of the patient and had different areas of his or her arm stroked by the experimenter, four of six patients stated that they could feel touch administered to the other individual in their own anesthetized arm. In two patients, when an ice cube was placed on the volunteer's hand, they could feel cold in their anesthetized arm. In addition, four of six patients reported referral from the contralateral intact limb to the anesthetized limb when touched by the experimenter. One patient felt cold referral.
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Interpretation
These data support that the mirror neuron system can act as a bridge connecting sensation both within an individual and between an individual and another person. However, additional studies are needed to fully understand the mechanisms behind this plasticity.
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Critical Care Medicine

Jean Mantz, M.D., Ph.D., Editor
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Severity of the compensatory antiinflammatory response determined by monocyte HLA-DR expression may assist outcome prediction in cirrhosis. Intensive Care Med 2011; 37:453–60

The major histocompatibility complex molecule human leukocyte antigen (HLA)-DR is reduced in patients with septic shock, and this has been used as a biomarker associated with susceptibility to infection and poor outcomes. Results from studies on HLA-DR concentrations in cirrhotic patients and clinical outcomes are variable. This cohort study was conducted to compare the expression of HLA-DR across patients with various degrees of cirrhosis severity, requiring intensive care unit (ICU) admission. In the first cohort, blood samples were taken from patients with confirmed cirrhosis. The second smaller cohort recruited only cirrhotic patients with recurrent refractory sepsis to compare immune responses with stable patients.
Cohort 1 included 100 patients who were stable, had acute-on-chronic liver disease, or were cirrhotic with multiple organ failure. Patients with either acute-on-chronic liver disease or cirrhotic with multiple organ failure had lower HLA-DR expression compared with stable patients (see fig. below). Concentrations in patients with stable cirrhosis were comparable with those in healthy controls (P > 0.05). An HLA-DR cutoff of 40% predicted survival to discharge, with a 59% sensitivity, an 80% specificity, and a 48% positive predictive value. Predictive accuracy was similar to that of Acute Physiology and Chronic Health Evaluation II and Sequential Organ Failure Assessment scores. In the second cohort, a reduced response to antigenic challenge was evident and an increased antiinflammatory cytokine profile was found.
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Interpretation
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Cirrhosis is associated with extremely poor prognosis in patients admitted into the ICU. Predictive markers of outcomes of cirrhotic ICU patients with sepsis are needed. In the current study, although an HLA-DR lower than 40% with absence of recovery predicted poor outcomes, the accuracy was not improved compared with Acute Physiology and Chronic Health Evaluation II and Sequential Organ Failure Assessment scores.
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Postintensive care unit psychologic burden in patients with chronic obstructive pulmonary disease and informal caregivers: A multicenter study. Crit Care Med 2011; 39:112–8

Patients with chronic obstructive pulmonary disease (COPD) are at least three times more likely to experience psychiatric disorders compared with the general population. Relatives of patients with COPD often experience similar psychiatric problems, such as anxiety and depression. A prospective multicenter study was conducted to assess the prevalence and risk factors of symptoms of psychiatric disorders among patients with COPD and their families after discharge from an ICU. Patients (n = 126) and their relatives (n = 102) completed the Hospital Anxiety and Depression Scale and the Peritraumatic Dissociative Experiences Questionnaire at ICU discharge and were interviewed by telephone at 90 days after discharge (53 patients and 47 relatives).
Overall, approximately half of patients experienced anxiety (52%) or depression (45.5%) at ICU discharge, with corresponding values of 72.2% and 25.7% in relatives, respectively. Both patients and their relatives continued to experience anxiety and depression 90 days after ICU discharge (see fig. below). Evidence of posttraumatic stress disorder–related symptoms was found in 20.7% of patients and 29.8% of relatives at day 90.
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Interpretation
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There is growing interest in the long-term consequences of ICU admission on patient cognition and behavior. Although this study has the limitations of a self-administered questionnaire, it emphasizes the degree of subjective disorders reported by both patients with COPD and their relatives after an ICU stay. Sleep disorders were reported by almost 70% of ICU patients. This study suggests that intensivists should pay attention to post-ICU psychiatric symptoms in both patients and relatives and consider prevention strategies.
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A prospective, randomized, double-blind, multicenter study comparing remifentanil with fentanyl in mechanically ventilated patients. Intensive Care Med 2011; 37:469–76

Analgesic pharmacodynamics may be altered dramatically in critically ill patients. Therefore, the particular opioids chosen to manage pain in these patients require special attention. This prospective, randomized, double-blind, multicenter study was conducted to assess potential differences between fentanyl and remifentanil in patients requiring intensive care therapy with mechanical ventilation. Patients received IV infusions of either fentanyl (0.02–0.08 μg · kg−1 · min−1) or remifentanil (0.1–0.4 μg · kg−1 · min−1) titrated up to the analgesia target based on a visual analog scale.
A priori, an interim analysis was planned after the first 60 patients were enrolled. Based on the results of this interim analysis (see fig. below), no differences between groups were observed in either primary or secondary end points. Because an additional 530 patients were required to demonstrate significance, the Independent Data Monitoring Committee decided that the study should be terminated.
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Interpretation
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This study, discontinued prematurely for futility, did not demonstrate any difference in the quality of analgesia and sedation or in any other outcome parameter between remifentanil and fentanyl in mechanically ventilated ICU patients. These results confirm and extend the view that good practice of analgesia and sedation in ICU patients consists of monitoring and titrating sedation and analgesia to effect, whatever the opioids and sedatives used.
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Nosocomial pneumonia in the intensive care unit acquired by mechanically ventilated versus nonventilated patients. Am J Respir Crit Care Med 2010; 182:1533–9

Patients in the ICU with hospital-acquired pneumonia have high morbidity and mortality rates. Increased knowledge of the potential differences between ventilator-assisted pneumonia or nonventilator ICU-acquired pneumonia may lead to improved treatments for these patients. Therefore, a prospective multicenter study of patients (N = 315) in the ICU for at least 48 h, with suspected hospital-acquired pneumonia, was conducted.
Patients with ventilator-assisted pneumonia had worse Acute Physiology and Chronic Health Evaluation II scores (17 vs. 15; P < 0.001) compared with patients with nonventilator ICU-acquired pneumonia. In patients with an identified microorganism, the proportion of pathogens was similar between groups. Hospital mortality was also similar between groups (see fig. below).
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Interpretation
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Studies on hospital-acquired pneumonia (that was not ventilator-assisted pneumonia) have shown higher rates of community-acquired and environmental pathogens and better outcomes than ventilator-assisted pneumonia. This study indicates that when such pneumonia is acquired in the ICU, pathogens and outcome are similar regardless of whether pneumonia was acquired during mechanical ventilation. These results emphasize that a patient's medical condition, rather than previous mechanical ventilation, determines the outcome of ICU-acquired pneumonias.
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Pain Medicine

Timothy J. Brennan, Ph.D., M.D., Editor
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Associations between pain and current smoking status among cancer patients. Pain 2011; 152:60–5

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Pain and smoking among cancer patients: The relationship is complex but the clinical implication is clear. Pain 2011; 152:10–1

Previous studies have demonstrated an association between smoking and reduced treatment outcomes; exacerbated symptoms, including pain; and poorer survival in patients with cancer. A cross-sectional study was conducted to examine associations between pain outcomes among cancer patients (N = 224) with varied smoking status.
Most patients (68%) had either breast or lung cancer, and all patients were fairly evenly distributed across disease stages. Pain severity was significantly different between never, former, and current smokers (P < 0.05), with current and former smokers experiencing more severe pain than never smokers. Among former smokers, an inverse relationship was observed between pain severity and pain interference and the number of years since quitting, regardless of cancer type. Differences were not observed among groups for pain-related distress. No correlation was found between the number of cigarettes smoked per day and pain severity, interference, or related distress.
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Interpretation
This study demonstrated a relationship between smoking and nonsmoking and pain, along with a relation between time since quitting and pain in patients with cancer. These data support previous studies suggesting that smoking status is positively associated with other chronic pain syndromes. The accompanying editorial suggests that aggressive promotion of smoking cessation in patients with cancer diagnoses may improve pain management.
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The comparative safety of opioids for nonmalignant pain in older adults. Arch Intern Med 2010; 170:1979–86

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The comparative safety of analgesics in older adults with arthritis. Arch Intern Med 2010; 170:1968–76

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The safety of opioid analgesics in the elderly: New data raise new concerns. Arch Intern Med 2010; 170:1986–8

There is a dearth of information regarding the comparative safety of nonsteroidal antiinflammatory drugs (NSAIDs) and opioids. Therefore, an observational study with propensity score matching comparing the safety of opioid therapy for nonmalignant pain in older adults was conducted. In addition, a retrospective review of Medicare beneficiaries was performed to compare the safety of nonselective NSAIDs, cyclooxygenase-2 inhibitors, and opioids in elderly patients with osteoarthritis or rheumatoid arthritis.
In the first study, all-cause 30-day mortality was increased in users of certain opioids; oxycodone and codeine carried greater risk. The risks of cardiovascular events, fracture, and gastrointestinal events differed between opioid groups and time points (see figs. A and B at top of next page for the 30- and 180-day points, respectively).
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Table 1
Table 1
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In the second study, all-cause mortality was higher among opioids users (hazard ratio, 1.87) compared with NSAID users. Compared with NSAIDs, opioids were associated with increased risk of cardiovascular events, fracture, and hospitalized safety event (table 1).
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Interpretation
These data challenge the concept that opioids may be safer in the elderly population with chronic pain. The accompanying editorial notes the limitations of such retrospective studies; however, the compelling association of increases in fractures in elderly patients prescribed opioids may be related to hormone suppression. Differences among opioids require further evaluation.
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Placebos without deception: A randomized controlled trial in irritable bowel syndrome. PLoS One 2010; 5:e15591

Table 2
Table 2
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Numerous studies have demonstrated the benefit of placebo treatments on both subjective and physiologic outcomes in multiple diseases, including irritable bowel syndrome. The current study assessed the effectiveness of an open-label placebo versus no treatment in patients (N = 80) with irritable bowel syndrome in a 3-week randomized controlled trial. Before randomization, patients were told that the placebo pills were inactive or “sugar pills.” At both the 11- and 21-day points, patients in the open-placebo group showed significant improvement in nearly all outcomes compared with the no-treatment group (table 2).
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Interpretation
This trial demonstrated beneficial outcomes of open-label placebo administration in patients with irritable bowel syndrome. The studies suggest that, for patients with diagnoses that are treated almost entirely based on subjective symptoms, the placebo effect can be strong. This may apply to some chronic pain syndromes as well.

© 2011 American Society of Anesthesiologists, Inc.

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