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Decreasing the Time to Administration of First Dose of Antibiotics in Children With Severe Sepsis

Mittal, Yash; Sankar, Jhuma; Dhochak, Nitin; Gupta, Samriti; Lodha, Rakesh; Kabra, Sushil Kumar

The Journal for Healthcare Quality (JHQ): January/February 2019 - Volume 41 - Issue 1 - p 32–38
doi: 10.1097/JHQ.0000000000000141
Original Article
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Objectives: To measure difference in median time to antibiotic administration in severe sepsis before and after making process changes and clinical outcomes such as duration of hospitalization and mortality.

Methods: The study was carried out in the emergency department in children <17 years of age with severe sepsis/septic shock. In phase 1, data were collected and reasons for delayed antibiotic administration were identified. Following this, process changes like creating a triage tool, re-enforcing the severe sepsis protocol and increasing the number of nurses were made to correct the delay. In phase 2, we measured outcomes to compare the effect of the process changes.

Results: A total of 28 and 13 children each were included during phase 1 and phase 2 of the study respectively. The median interquartile range time to administration of antibiotics from the time of admission decreased significantly from 50 minutes (18, 65) to 20 minutes (15, 20) (p = .02). Duration of hospital stay was longer in phase 1 as compared to phase 2 (12 days vs. 6 days). However, the difference was not statistically significant (p = .1).

Conclusions: Use of a triage tool, severe sepsis protocol, and increasing the number of nurses resulted in earlier recognition and administration of first dose of antibiotics in children with severe sepsis.

For more information on this article, contact Jhuma Sankar at jhumaji@gmail.com.

Funders: ICMR, Short Term Student Scholarship 2016.

The authors declare no conflict of interest.

Supplemental digital content is available for this article. Direct URL citations appear in the printed text and in the HTML and PDF versions of the article at www.jhqonline.com.

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Introduction

Severe sepsis and septic shock are important causes of morbidity and mortality worldwide.1–5 Mortality in children has been reported to be 10–13% in developed countries and may vary from 25% to 60% in resource restricted countries.3–8 Early detection and timely administration of appropriate antibiotics are important factors that have shown to improve outcomes in patients with sepsis.9–11

In severe sepsis, the exaggerated immune response to the infectious agent results in multiorgan dysfunction and ultimately death if left untreated. Antibiotics by virtue of their bactericidal activity may halt this physiologic progression to multi organ dysfunction syndrome.12,13 Antibiotics should ideally be given before hypotension occurs in severe sepsis because irreversible injury may result.9–11 However, the initial signs and symptoms of sepsis are frequently nonspecific, leading to a delay in diagnosis. If the child is in shock, the focus is on resuscitating in the first hour rather than administration of antibiotics.9,10,14–16

It is well recognized now that delays in recognition and resuscitation are common in emergency room (ER). Such delays are associated with increased mortality in patients with septic shock.7–9,14,15 The average time to administration of antibiotics reported across few studies has been between 90 and 130 minutes.9–11,13,17 Delay in administration may result in increased mortality rates.9–11 Study site data suggest a delay in administration of antibiotics from the time of recognition of severe sepsis.

The effects of early initiation of antibiotic on outcomes such as mortality, duration of hospital stay, and vasoactive-free period were measured in few studies.9–11,13,17 Unfortunately, there are no studies reported to date, in children admitted to health care settings from resource-restricted countries on the timing of antibiotic administration and factors causing such delays. To address these knowledge gaps and to assess our practices and improve them, we undertook this quality improvement initiative over a period of 6 months. Our goal was to systematically assess the time to antibiotic administration, the reasons for such delay, and make process changes to ensure timely administration of antibiotics. We aimed to decrease the time to administration of first dose of antibiotics to within an hour of diagnosis of severe sepsis in all children requiring admission.

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Methods

Aim and Objectives

The overall aim of our study was to reduce the time to administration of first dose of antibiotics. The Plan, Do, Study, Act (PDSA) aim was to administer first dose of antibiotics within the first hour of recognition of severe sepsis. Accordingly, our objectives were—(1) to measure process outcome measures such as difference in mean/median time to administration of antibiotics before and after making the process changes and (2) to measure clinical outcome measures such as duration of hospitalization and mortality among others.

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Study Design, Setting, and Participants

The study was carried out in the ER of our tertiary care hospital from April 2016 to September 2016. This was a quality improvement before and after study. Children aged 2 months to 17 years of age with severe sepsis were eligible for enrollment. Children already on antibiotics and those whose parents refused informed consent were excluded. The study was approved by the Institute Ethics Committee. We also obtained waiver of informed consent in view of noninterventional nature of the study.

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Outcomes and Their Definitions and Measurement

The primary process outcome evaluated was the time to administration of first dose of antibiotics from the time of recognition of severe sepsis. This was measured from the time the patient was diagnosed to have severe sepsis by the resident on duty to the time the nurse administered the first dose of antibiotics. The other process outcomes measured were—(1) time to recognition of severe sepsis (measured from the time the child presented to the ER to the diagnosis of severe sepsis by the resident on duty) and (2) time to administration of first bolus (measured from the time of recognition of septic shock to administering the first fluid bolus) in children with septic shock. The clinical outcomes measured were duration of hospital stay and mortality.

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Study Definitions

We used the following definitions for the purpose of the study. Severe sepsis was defined as sepsis induced tissue hypoperfusion or organ dysfunction (acute lung injury, acute kidney injury, coagulopathy, increased bilirubin, and/or thrombocytopenia). Septic shock was defined as sepsis-induced hypotension despite adequate fluid resuscitation.18

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Description of Intervention, Study Tools and Their Evolution

The study was led by the team of one consultant (J.S.), three residents, and three nurses in the pediatric ER, which is equipped with eight beds. The average number of patients presenting to the ER is 100–150 patients per day.

The project was carried out in three phases. We used the PDSA cycle of quality improvement methodology in each phase. The components of the PDSA cycle used for the study are described in Appendix 1 (see Figure, Supplemental Digital Content 1, http://links.lww.com/JHQ/A58).

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Phase One

In the first phase, carried out over 2 months, data collection strategies were developed. The data included: time to administration of first dose of antibiotics, reasons for delay in administration of first dose of antibiotics, time of presentation to ER, time to attachment of monitor, time to initiation of first fluid bolus, duration of antibiotic therapy, duration of hospital stay, and mortality. These data were collected on a sepsis collection tool designed for the study. Data were analyzed. We also tried to identify important process barriers in cases of delay in administering antibiotics using the fish bone diagram. Figure 1 depicts the important process barriers identified. The process barriers identified were shortage of nurses, triage personnel, and lack of space for triaging among others. Patient-related factors identified were difficulty in obtaining intravenous access and delay in initiating resuscitation. Delayed recognition due to atypical presentation of the patient was responsible for delay in initiating resuscitation in few patients.

Figure 1

Figure 1

After phase 1 data were collected, the team implemented the following changes: increased the number of nurses, provided space for triage, and created a triage tool for severe sepsis (see Table, Supplemental Digital Content 2, http://links.lww.com/JHQ/A59) for recognizing patients with severe sepsis, which took less than a minute to fill.18,19 We also educated the residents on insertion of intraosseous access for difficult access and reinforced the use of sepsis care protocol (see Table, Supplemental Digital Content 3, http://links.lww.com/JHQ/A60) with timed interventions. The important components of the protocol included identifying signs of severe sepsis in the first 10 minutes, establishing vascular access and administering fluid bolus within first 15 minutes, administering antibiotics in the first hour and initiating vasoactive therapy in cases of fluid refractory shock within the first hour. We trained the treating team and made them familiar with the process changes and stressed the need to ensure compliance with the same. Following the training, we again observed practices over 2 weeks (first and second weeks of July) and identified the problems with implementation of the protocol. This time the process barriers were only the atypical presentation in 2 of the 8 cases who presented to the ER (one was on steroids and was afebrile and the other patient was a case of asthma [with lower respiratory tract infection]). The difficulty in IV access was improving and in only one patient it was delayed (15 minutes). We again reinforced the need for and technique of intraosseous access to overcome this barrier.

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Phase 2

During this phase, we collected data over a period of 2 months (August, September 2016) to compare the effect of the changes made.

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Statistical Analysis

Data were entered into Microsoft Excel 2013 and analyzed using Stata 11 (Stata Corp, College Station, TX). Categorical data are represented as number (%) while continuous variables are presented as mean (SD), if normally distributed and median (interquartile range), if skewed. Statistical analysis was performed using Student's t test/Wilcoxon rank sum test and chi-square test for continuous and categorical variables, respectively. p-value of <0.05 is considered significant.

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Results

A total of 46 and 24 children presented with severe sepsis during phase 1 and phase 2 of the study respectively. Of these, 28 and 13 were already on antibiotics at the time of presentation to ER and therefore had to be excluded. The baseline characteristics of the children admitted during these two phases were comparable (Table 1). The median age of presentation was 5 years in phase 1 while it was 0.9 years in phase 3. Both phases had male preponderance. Pneumonia was the most common cause of infection in both phases (33% vs. 46%) followed by abdominal infection (17% vs. 23%). Underlying illnesses were present in 61% of the patients in both phases.

Table 1

Table 1

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Process Outcomes

The median time to administration of antibiotics decreased from 50 (18, 65) minutes in phase 1 to 20 (15, 20) minutes (p = .02) in phase 3 (Figure 2A). The median time to recognition of severe sepsis from the time of presentation to ER decreased significantly from 10 (5, 15) minutes to 5 (2, 5) minutes after making the process changes (p = .003) (Figure 2B). Only 1 out of 13 children received antibiotics beyond the first hour in PHASE 2 as compared to five children in the initial phase. The median time to administration of first fluid bolus was 10 minutes in both phases while the time to attach monitors was 21 minutes and 27 minutes in phase 1 and phase 2, respectively (Table 2). The difference was not statistically significant.

Figure 2

Figure 2

Table 2

Table 2

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Clinical Outcomes

The mean (SD) duration of hospital stay was 12 days (5) in phase 1 patients while it was 6 (2) days in phase 2. This difference however was not statistically significant. Two children died in each phase of refractory septic shock (Table 2).

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Limitations

The strength of our study is that we used a quality improvement initiative to improve the process outcomes such as decreasing the time to antibiotic administration in children with severe sepsis and/or septic shock. After implementing a simple triage tool, sepsis protocol, and increasing the number of nurses, we observed a decrease in time to administration of the first dose of antibiotics to within one hour of sepsis recognition.

The important limitations of our study include the small number of patients and the short time frame that makes it difficult to draw conclusions related to the impact of early antibiotic administration on clinical outcomes in children with severe sepsis or septic shock. Another limitation is that it was conducted in a unit where patients are evaluated as soon as they walk into the ER and treatment is initiated without any delay even before formalities for admission can be completed. Also, antibiotics are readily available in the ER at any point of time or can be made available without any delay from the pharmacy of the hospital free of cost. Our processes may not be congruent with hospital ER throughout where treatment is initiated only after completing registration and admission.

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Discussion

The importance of timely administration of antibiotics in patients of severe sepsis and septic shock is well known.9–11 The Surviving Sepsis Campaign Guideline 2012 recommends administration of appropriate antibiotics within the first hour of initiating resuscitation.19 Whether this recommendation is followed has been the research focus of several studies in adults and few pediatric studies as well.9–11,14–16

In this quality improvement before and after initiative, after introduction of changes in the system using components of Quality Improvement, we observed that—(1) the median time to recognition of severe sepsis decreased from 10 to 5 minutes, (2) the median time to administration of antibiotics reduced to 20 minutes from a baseline of 50 minutes, and (3) the duration of hospital stay was only 6 days in phase 2 as compared to 12 days in phase 1.

Weiss et al,11 in a retrospective chart review of 135 children admitted to the Pediatric Intensive Care Unit of a tertiary care teaching hospital of a developed country, observed the median time to administration of antibiotics to be 140 minutes (interquartile range: 74–277 minutes). Delay in antibiotics in phase 1 was less than reported by Weiss et al (phase 1: [median] 50 minutes vs. Weiss et al11:140 minutes). The time to administration of antibiotics from triaging or from recognition of severe sepsis and septic shock is reported to range from 90 to 120 minutes in acutely ill adult patients9–11,13,17 from settings similar to that of Weiss et al.11,14–16 The early administration of antibiotics in our unit in phase 1 even before the system changes were made may be explained by the high incidence of sepsis in developing countries like ours. As a result of this, the index of suspicion for sepsis is high resulting in early evaluation and treatment of these patients.

Weiss et al11 observed patients with more than 3 hours delay to have OR of mortality of 3.92 (95% CI: 1.27 to 12.06). This association remained significant after adjusting for illness severity as well. They also observed fewer organ failure free days in those receiving antibiotics beyond the first 3 hours. Similar findings have been reported in few other studies with odds of mortality between 1.6 and 3 times the risk beyond the first hour for up to 3 hours.9–11,17,20 Beyond the fifth hour, the risk of mortality varied from 1.38 to 15 times. However, we did not find any association between time to administration of antibiotics and mortality in phase 1 of our study. This was probably due to the small numbers and because of increased sensitization to sepsis and early intervention, which has been mentioned earlier. Larger studies in different settings would be required to estimate the true effect of delayed administration of antibiotics on mortality in resource-limited countries.

The effect of time to appropriate antibiotic therapy has been shown to be an independent determinant of length of stay in the Intensive Care Unit and in-hospital.17 David et al observed that for every hour delay in initiating appropriate antibiotic therapy, the length of Intensive Care Unit stay and hospital stay increased by 0.095 days and 0.13 days, respectively. Similar to their study, we observed the length of hospital stay to be longer in phase 1 as compared to phase 2 following the Quality Improvement initiative even though the difference was not statistically significant. It appears that there has been a reduction in length of stay following the training and process changes. However, whether delay in administering antibiotics increased the duration of hospital stay will have to be evaluated in larger studies in resource restricted settings to confirm such association.

The major hurdles causing delay in antibiotic administration in phase 1 of our study were overcrowding, high patient load, difficult IV access, and atypical presentation leading to delayed recognition of severe sepsis similar to what has been previously reported.9–11,14–17,20 We recorded shortage of nurses in phase 1 to be a hurdle in early initiation of antibiotics in the ER. Shortage of nursing staff is reported to affect health care quality and patient outcomes adversely. It also causes burnout and job dissatisfaction among nurses.21–25 We could overcome this in phase 3 by increasing the number of nurses in the ER who helped in screening the patients earlier, managing the crowd more effectively and administering antibiotics without delay.

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Conclusions

Use of a triage tool, severe sepsis protocol, and increasing the number of nurses in the ER as part of a quality improvement initiative resulted in earlier recognition of severe sepsis and substantial reduction in time to administration of first dose of antibiotics in children with severe sepsis. Studies with larger sample size would be required to show the true impact of such reduction in time to recognition or antibiotic administration on important clinical outcomes such as mortality or hospital stay.

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Implications

  • The project helped reduce the time taken to administer antibiotics which is an important component of goal directed therapy in severe sepsis/septic shock.
  • It also helped understand the important process barriers that existed in the system and helped identify possible solutions to overcome these barriers and sustain the changes.
  • Implementation of a simple triage tool and a severe sepsis protocol helped identify and treat these patients earlier.
  • Increasing the number of nurses helped in managing the crowd more effectively and initiating treatment early.
  • These changes we believe would help improve the process barriers to management of other acute illnesses as well and not only patients with severe sepsis/septic shock in our ER.
  • We also observed the duration of Pediatric Intensive Care Unit stay to be shorter in those receiving the antibiotics early even though this was not statistically significant.
  • Our study results are hypothesis generating and would need further evaluation with larger numbers to confirm or refute this or other associations with timing of antibiotic administration.
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References

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2. Artero A, Zaragoza R, Nogueira JM. Epidemiology of Severe Sepsis and Septic Shock, Severe Sepsis and Septic Shock—Understanding A Serious Killer. Ricardo Fernandez Dr, ed. InTech; 2012. http://www.intechopen.com/books/severe-sepsis-and-septic-shock-understanding-a-serious-killer/epidemiology-of-severe-sepsis-and-septic-shock. Accessed December 21, 2017.
3. Watson RS, Carcillo JA, Linde-Zwirble WT, Clermont G, Lidicker J, Angus DC. The epidemiology of severe sepsis in children in the United States. Am J Respir Crit Care Med. 2003;167:695–701.
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Authors' Biographies

Yash Mittal, MBBS, AIIMS, New Delhi, VI semester Medical Student involved in research projects on improving quality of care in patient care areas.

Jhuma Sankar, MD (Paed), AIIMS, New Delhi; Assistant Professor; Division of Paediatric Pulmonology and Critical Care; As a Pediatric Intensivist, she is involved in care of sick children admitted in intensive care unit at AIIMS, Delhi. She has conducted multiple studies exploring different aspects on management of septic shock in children and has published the results in major indexed journals on critical care.

Nitin Dhochak, MD (Paed), AIIMS, New Delhi; Senior Resident; Division of Pediatric Pulmonology and Critical Care; Currently pursuing DM course in pediatric pulmonology and critical care, Dr. Nitin is involved in care of critically ill children and children with chronic/acute respiratory illnesses. He is also involved in various quality improvement projects in the unit in patient care areas.

Samriti Gupta, MD (Paed), AIIMS, New Delhi; Senior Resident; Division of Pediatric Pulmonology and Critical Care; Currently pursuing DM course in pediatric pulmonology and critical care, Dr. Samriti is involved in care of critically ill children and children with chronic/acute respiratory illnesses. She is also involved in various quality improvement projects in the unit in patient care areas.

Rakesh Lodha, MD (Paed), AIIMS, New Delhi; Professor; Division of Paediatric Pulmonology and Critical Care; As chief of Division of Paediatric Intensive care unit at AIIMS, Dr. Lodha has been instrumental in revolutionizing Pediatric critical care in India alongside others. He is an expert in research methodology and has over 300 publications in reputed national and international journals. He has contributed to national and international health care policy and guidelines with his path breaking research on critical illnesses, infections, tuberculosis, and HIV.

S K Kabra, MD (Paed), AIIMS, New Delhi; Professor and Chief; Division of Paediatric Pulmonology and Critical Care; Known as the “Founder of pediatric pulmonology” in India and also well known abroad as an expert in pediatric pulmonology, Dr. Kabra as the head of division of pediatric pulmonology has revolutionized the care of children with pulmonary diseases in India. His research work has been practice changing for chronic lung diseases, cystic fibrosis, tuberculosis, and chest diseases. He cherishes the vision of improving healthcare for children in India and is a key member of national health care policy and guideline making bodies.

Keywords:

early recognition; antibiotic administration; delayed administration of antibiotics; severe sepsis; septic shock

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