Electronic Supplemental Material
Effect of rapid response systems on hospital mortality,
A systematic review and meta-analysis
Running title: Rapid Response System and Hospital Mortality
Audrey De Jong 1*, Boris Jung 1-2*, Aurelien Daurat 1, Gerald Chanques 1-2, Martin Mahul 1, Marion Monnin 1, Nicolas Molinari 3, Samir Jaber 1-2
Authors affiliations:
1 Intensive Care Unit, Department of Anesthesia and Critical Care Medicine, University of Montpellier, Saint Eloi Teaching Hospital, 80 avenue AugustinFliche, F-34295 Montpellier, Cedex 5, France
2Centre National de la Recherche Scientifique (CNRS 9214) - Institut National de la Santé et de la Recherche Medicale (INSERM U-1046), Montpellier University, Montpellier, France
3 Department of Statistics, University of Montpellier Lapeyronie Hospital, UMR 729 MISTEA, Montpellier, France
* Contributed equally to the study.
Corresponding author:
Samir Jaber
Intensive Care Unit, Anesthesia and Critical Care Department
Saint Eloi Teaching Hospital
80 Av Fliche
34295 Montpellier Cedex 5
France
Phone: (33) 4-67-33-72-71
Fax: (33) 4-67-33-74-48
E-mail:
Authors conflicts of interest
Boris Jung reports personal fees from Merck (Whitehouse station, NJ) and Astellas (Tokyo, Japan) without relations with the present study, AurelienDaurat has nothing to disclose; Nicolas Molinari has nothing to disclose; Audrey De Jong, Martin Mahul, Marion Monnin, Gerald Chanques, Nicolas Molinarihave nothing to disclose; Samir Jaber reports personal fees from Maquet, Draeger, Hamilton Medical, Fisher Paykel and Abbott without relations with the present study.
Source of funding: This study was supported by the University Hospital of Montpellier.
Key words: Medical Emergency Team, Rapid Response Systems, Meta-analysis, Patient safety
Introduction
The aim of the present study was to conduct an updated meta-analysis to evaluate the effect of RRSon hospital mortality.
We hypothesized that the implementation of a MET would improve the overall and unexpected hospital mortality.
Methods
This article reports our meta-analysis and systematic review of studies of RRScompared to no-RRSin accordance with the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) statement.[25]
Search strategy
We performed a computerized search of MEDLINE (1966 to July 31, 2015), EMBASE (1977 to July 31, 2015) and the Cochrane Center Register of Controlled Trials (CENTRAL) (1943 to July 31, 2015) for studies comparing RRS to no-RRS regarding the total hospital adult mortality and the unexpected hospital mortality. For the bibliographic review, keywords (“rapid response team”, “rapid response system”, “hospital mortality”, “unexpected mortality”, "medical emergency team", "critical care outreach"), medical subject headings ("quality improvement", "mortality", "intensive care unit" and "critical care") and Emtree terms (“rapid response team”, "rapid response system", "RRT" and “RRS”) were used in our Boolean search strategy. We identified and deleted any duplicate papers. All potentially eligible papers were retrieved in full. References in the retrieved articles were also examined for relevant publications.
Selection criteria and outcome measures
We screened for relevant studies that compared the rate of total hospital adult mortality and unexpected mortality between RRS and no-RRS.
Then we made a quantitative synthesis performing a meta-analysis and systematic review. For this purpose, we selected the following study designs: randomized controlled trials, prospective observational studies (before and after treatment) and retrospective observational studies.
The primary endpoint of this meta-analysis was the incidence of overall hospital mortality. The secondary endpoint was the incidence of unexpected mortality.
We included studies reporting at least one clinical outcome of interest to perform a meta-analysis.
Data collection and analysis
First, two authors (AD and BJ) independently screened the retrieved studies by title and then by abstract for exclusion. They assessed the full text of the possible relevant studies for inclusion and exclusion criteria. Disagreement was resolved by discussion and arbitrated if necessary by a third author (ADJ). Data were then added to an excel database, specifically designed for this review and analysed in RevMan 5.3 software.
Statistical analysis
Data were extracted as they were reported in the original paper or based on the answers of the authors to our queries. Included studies were appraised for their risk of bias by two authors (ADJ, NM) using the Cochrane Collaboration’s tool[26] for assessing risk of bias in randomized controlled trialsand the Newcastle-Ottawa Scale[27] for assessing risk of bias in observational studies. We used fixed or random effects models, depending on statistical heterogeneity between studies.[28] We used odds ratio (OR) as the summary measure for dichotomous outcomes. Statistical heterogeneity was quantified by the Q-Cochrane heterogeneity test (Q statistic with degree of freedom (df)) and the I² statistic[27]. In case of heterogeneity, a random effect model was performed.Predefined subgroups analysis and exclusion of outlying studies were performed to reduce heterogeneity for the primary outcome.4,5.(référence de la cochrane + Hole Lancet 2015)To assess the effect of potential confounding factors (adjustment of OR or not, multiple or single center study, prospective or retrospective study, single afferent limb, multiple afferent limb, physician lead team efferent limb for the main endpoint (unexpected hospital mortality) we performed a meta-regression using the restricted maximum likelihood estimate method, a recommended random effect approach that accounts for residual between-trial heterogeneity[29] using the Comprehensive Meta-Analysis 3.0 software.
A funnel plot (plot of treatment effect against trial precision) was also created to determine the presence of publication bias, true heterogeneity, data irregularities and choice of effect measure in the meta-analysis. The funnel plot is skewed and asymmetrical in case of bias that usually leads to an overestimate of the treatment effect.
Results
The updated literature search identified 10additionalstudies to the work of Winters et al[7]including the present study to provide a total of 31studies and 10,544,745 patients (detailed flow chart is provided in the appendix: Figure S1).Of those, 9 studies (1,045,364 patients) provided data on unexpected mortality and 32 studies (9,517,719 patients)reported overall mortality rate. The meta-regression did not reveal any significant effect of potential confounding factors (adjustment of OR or not (P = 0.55), multiple or single centre study (P = 0.10), prospective or retrospective study (P = 0.99), single afferent limb (P = 0.08), multiple afferent limb (P = 0.89), physician lead team efferent limb (P = 0.54)) for overall hospital mortality.
RRS were associated with a significant decrease in both overall hospital mortality (OR 0.89; 95% CI 0.85-0.93 (Figure1A.) andunexpected mortality (OR 0.51; 95% CI (0.35-0.76) (Figure1B.). The overall test for heterogeneity among studies was statistically significant both for overall and unexpected mortality analysis (P< 0.001). Funnel plots did not reveal publication bias for overall mortality or unexpected mortality (Figure S2 and S3).Subgroups analysis performed according to the multicentric or monocentric design (FigureS4), the prospective or retrospective design (Figure S5) and the location of the studies (Figure S6) showed consistent results, with a significant decrease of overall hospital mortality. After exclusion of outlying studies (Figure S7), heterogeneity became low and a fixed model could be applied, showing identical results with a decreased incidence of overall hospital mortality (OR 0.92; 95% CI (0.90-0.94).
Discussion
In this updated systematic review and meta-analysis, MET implementation was associated with a significant decrease in overall and unexpected mortality of hospitalized patients.One limitation was the large amount of statistical heterogeneity. Nevertheless, we considered that to combine data using a random effect meta-analysis would allow a more useful result than to include a small number of homogeneous studies as presented in Figure S7. (Hole Lancet 2015) Moreover, subgroups analysis and exclusion of outlying studies allowing reducing heterogeneity showed similar results.Until now, the effect of RRS on mortality remains debated with several discordant studies.[60]The meta-analysispublished by Chan et al in 2010reporteda reduction in cardiac arrest ratebut no significant effect on mortality.[6]More recently, the updated review by Winters et al suggested a positive impact on patients outcome, howeverthe statistical significance was not reached.[7]In this setting, the present updated systematic review is a substantial contribution, because itstrongly suggests a positive effect of RRSon overall and unexpected mortality.
1
References
1. Brennan TA, Leape LL, Laird NM, et al. (1991) Incidence of adverse events and negligence in hospitalized patients. Results of the Harvard Medical Practice Study I. N Engl J Med 324:370–376. doi: 10.1056/NEJM199102073240604
2. Zegers M, de Bruijne MC, de Keizer B, et al. (2011) The incidence, root-causes, and outcomes of adverse events in surgical units: implication for potential prevention strategies. Patient Saf Surg 5:13. doi: 10.1186/1754-9493-5-13
3. Berwick DM, Calkins DR, McCannon CJ, Hackbarth AD (2006) The 100,000 lives campaign: setting a goal and a deadline for improving health care quality. JAMA 295:324–327. doi: 10.1001/jama.295.3.324
4. Priestley G, Watson W, Rashidian A, et al. (2004) Introducing Critical Care Outreach: a ward-randomised trial of phased introduction in a general hospital. Intensive Care Med 30:1398–1404. doi: 10.1007/s00134-004-2268-7
5. Hillman K, Chen J, Cretikos M, et al. (2005) Introduction of the medical emergency team (MET) system: a cluster-randomised controlled trial. Lancet 365:2091–2097. doi: 10.1016/S0140-6736(05)66733-5
6. Chan PS, Jain R, Nallmothu BK, et al. (2010) Rapid Response Teams: A Systematic Review and Meta-analysis. Arch Intern Med 170:18–26. doi: 10.1001/archinternmed.2009.424
7. Winters BD, Weaver SJ, Pfoh ER, et al. (2013) Rapid-Response Systems as a Patient Safety StrategyA Systematic Review. Ann Intern Med 158:417–425. doi: 10.7326/0003-4819-158-5-201303051-00009
8. Jones D, Bellomo R, DeVita MA (2009) Effectiveness of the Medical Emergency Team: the importance of dose. Crit Care Lond Engl 13:313. doi: 10.1186/cc7996
9. England K, Bion JF (2008) Introduction of medical emergency teams in Australia and New Zealand: a multicentre study. Crit Care 12:151. doi: 10.1186/cc6902
10. Institute for Healthcare Improvement: Overview. Accessed 9 Oct 2014
11. Hilton AK, Jones D, Bellomo R (2013) Clinical review: The role of the intensivist and the rapid response team in nosocomial end-of-life care. Crit Care 17:224. doi: 10.1186/cc11856
12. Salvatierra G, Bindler RC, Corbett C, et al. (2014) Rapid response team implementation and in-hospital mortality*. Crit Care Med 42:2001–2006. doi: 10.1097/CCM.0000000000000347
13. von Elm E, Altman DG, Egger M, et al. (2007) The Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) Statement: Guidelines for Reporting Observational Studies. Ann Intern Med 147:573–577. doi: 10.7326/0003-4819-147-8-200710160-00010
14. Cummins RO, Chamberlain D, Hazinski MF, et al. (1997) Recommended guidelines for reviewing, reporting, and conducting research on in-hospital resuscitation: the in-hospital “Utstein style”. American Heart Association. Circulation 95:2213–2239.
15. Devita MA, Bellomo R, Hillman K, et al. (2006) Findings of the first consensus conference on medical emergency teams. Crit Care Med 34:2463–2478. doi: 10.1097/01.CCM.0000235743.38172.6E
16. de Jong A, Molinari N, de Lattre S, et al. (2013) Decreasing severe pain and serious adverse events while moving intensive care unit patients: a prospective interventional study (the NURSE-DO project). Crit Care 17:R74. doi: 10.1186/cc12683
17. Taylor MJ, McNicholas C, Nicolay C, et al. (2014) Systematic review of the application of the plan-do-study-act method to improve quality in healthcare. BMJ Qual Saf 23:290–298. doi: 10.1136/bmjqs-2013-001862
18. Chan PS, Khalid A, Longmore LS, et al. (2008) Hospital-wide code rates and mortality before and after implementation of a rapid response team. JAMA 300:2506–2513. doi: 10.1001/jama.2008.715
19. Subbe CP, Kruger M, Rutherford P, Gemmel L (2001) Validation of a modified Early Warning Score in medical admissions. QJM Mon J Assoc Physicians 94:521–526.
20. Jaber S, Jung B, Corne P, et al. (2010) An intervention to decrease complications related to endotracheal intubation in the intensive care unit: a prospective, multiple-center study. Intensive Care Med 36:248–255. doi: 10.1007/s00134-009-1717-8
21. Haig KM, Sutton S, Whittington J (2006) SBAR: a shared mental model for improving communication between clinicians. Jt Comm J Qual Patient Saf Jt Comm Resour 32:167–175.
22. MCO : Classification médico-économique | ATIH. Accessed 13 Apr 2015
23. Le Gall JR, Lemeshow S, Saulnier F (1993) A new Simplified Acute Physiology Score (SAPS II) based on a European/North American multicenter study. JAMA J Am Med Assoc 270:2957–2963.
24. Vincent JL, Moreno R, Takala J, et al. (1996) The SOFA (Sepsis-related Organ Failure Assessment) score to describe organ dysfunction/failure. On behalf of the Working Group on Sepsis-Related Problems of the European Society of Intensive Care Medicine. Intensive Care Med 22:707–710.
25. Liberati A, Altman DG, Tetzlaff J, et al. (2009) The PRISMA statement for reporting systematic reviews and meta-analyses of studies that evaluate healthcare interventions: explanation and elaboration. BMJ 339:b2700.
26. Higgins JG Cochrane handbook for systematic reviews of interventions version 5.1.0. The cochrane collaboration.
27. Wells GS, O’Connell D, Peterson J, et al. The Newcastle-Ottawa Scale (NOS) for assessing the quality of nonrandomized studies in metaanalyses.
28. Mesgarpour B, Heidinger BH, Schwameis M, et al. (2013) Safety of off-label erythropoiesis stimulating agents in critically ill patients: a meta-analysis. Intensive Care Med 39:1896–1908. doi: 10.1007/s00134-013-3030-9
29. Thompson SG, Sharp SJ (1999) Explaining heterogeneity in meta-analysis: a comparison of methods. Stat Med 18:2693–2708.
30. Bristow PJ, Hillman KM, Chey T, et al. (2000) Rates of in-hospital arrests, deaths and intensive care admissions: the effect of a medical emergency team. Med J Aust 173:236–240.
31. Buist MD, Moore GE, Bernard SA, et al. (2002) Effects of a medical emergency team on reduction of incidence of and mortality from unexpected cardiac arrests in hospital: preliminary study. BMJ 324:387–390.
32. Bellomo R, Goldsmith D, Uchino S, et al. (2003) A prospective before-and-after trial of a medical emergency team. Med J Aust 179:283–287.
33. Kenward G, Castle N, Hodgetts T, Shaikh L (2004) Evaluation of a medical emergency team one year after implementation. Resuscitation 61:257–263. doi: 10.1016/j.resuscitation.2004.01.021
34. Jones D, Bellomo R, Bates S, et al. (2005) Long term effect of a medical emergency team on cardiac arrests in a teaching hospital. Crit Care 9:R808–R815. doi: 10.1186/cc3906
35. Dacey MJ, Mirza ER, Wilcox V, et al. (2007) The effect of a rapid response team on major clinical outcome measures in a community hospital*: Crit Care Med 35:2076–2082. doi: 10.1097/01.CCM.0000281518.17482.EE
36. Baxter AD, Cardinal P, Hooper J, Patel R (2008) Medical emergency teams at The Ottawa Hospital: the first two years. Can J Anaesth J Can Anesth 55:223–231. doi: 10.1007/BF03021506
37. Campello G, Granja C, Carvalho F, et al. (2009) Immediate and long-term impact of medical emergency teams on cardiac arrest prevalence and mortality: a plea for periodic basic life-support training programs. Crit Care Med 37:3054–3061. doi: 10.1097/CCM.0b013e3181b02183
38. Konrad D, Jäderling G, Bell M, et al. (2010) Reducing in-hospital cardiac arrests and hospital mortality by introducing a medical emergency team. Intensive Care Med 36:100–106. doi: 10.1007/s00134-009-1634-x
39. Lighthall GK, Parast LM, Rapoport L, Wagner TH (2010) Introduction of a rapid response system at a United States veterans affairs hospital reduced cardiac arrests. Anesth Analg 111:679–686. doi: 10.1213/ANE.0b013e3181e9c3f3
40. Santamaria J, Tobin A, Holmes J (2010) Changing cardiac arrest and hospital mortality rates through a medical emergency team takes time and constant review. Crit Care Med 38:445–450. doi: 10.1097/CCM.0b013e3181cb0ff1
41. Sarani B, Palilonis E, Sonnad S, et al. (2011) Clinical emergencies and outcomes in patients admitted to a surgical versus medical service. Resuscitation 82:415–418. doi: 10.1016/j.resuscitation.2010.12.005
42. Shah SK, Cardenas VJ, Kuo Y-F, Sharma G (2011) Rapid response team in an academic institution: does it make a difference? Chest 139:1361–1367. doi: 10.1378/chest.10-0556
43. Beitler JR, Link N, Bails DB, et al. (2011) Reduction in hospital-wide mortality after implementation of a rapid response team: a long-term cohort study. Crit Care 15:R269. doi: 10.1186/cc10547
44. Laurens N, Dwyer T (2011) The impact of medical emergency teams on ICU admission rates, cardiopulmonary arrests and mortality in a regional hospital. Resuscitation 82:707–712. doi: 10.1016/j.resuscitation.2010.11.031
45. Sabahi M, Fanaei SA, Ziaee SA, Falsafi FS (2012) Efficacy of a rapid response team on reducing the incidence and mortality of unexpected cardiac arrests. Trauma Mon 17:270–274. doi: 10.5812/traumamon.4170
46. Howell MD, Ngo L, Folcarelli P, et al. (2012) Sustained effectiveness of a primary-team–based rapid response system*: Crit Care Med 40:2562–2568. doi: 10.1097/CCM.0b013e318259007b
47. Tobin AE, Santamaria JD (2012) Medical emergency teams are associated with reduced mortality across a major metropolitan health network after two years service: a retrospective study using government administrative data. Crit Care Lond Engl 16:R210. doi: 10.1186/cc11843
48. Al-Qahtani S, Al-Dorzi HM, Tamim HM, et al. (2013) Impact of an intensivist-led multidisciplinary extended rapid response team on hospital-wide cardiopulmonary arrests and mortality. Crit Care Med 41:506–517. doi: 10.1097/CCM.0b013e318271440b
49. Karpman C, Keegan MT, Jensen JB, et al. (2013) The impact of rapid response team on outcome of patients transferred from the ward to the ICU: a single-center study. Crit Care Med 41:2284–2291. doi: 10.1097/CCM.0b013e318291cccd
50. Chen J, Ou L, Hillman K, et al. (2014) The impact of implementing a rapid response system: A comparison of cardiopulmonary arrests and mortality among four teaching hospitals in Australia. Resuscitation 85:1275–1281. doi: 10.1016/j.resuscitation.2014.06.003
51. Segon A, Ahmad S, Segon Y, et al. (2014) Effect of a rapid response team on patient outcomes in a community-based teaching hospital. J Grad Med Educ 6:61–64. doi: 10.4300/JGME-D-13-00165.1
52. Moriarty JP, Schiebel NE, Johnson MG, et al. (2014) Evaluating implementation of a rapid response team: considering alternative outcome measures. Int J Qual Health Care J Int Soc Qual Health Care ISQua 26:49–57. doi: 10.1093/intqhc/mzt091
53. Kwak HJ, Yun I, Kim S-H, et al. (2014) The extended rapid response system: 1-year experience in a university hospital. J Korean Med Sci 29:423–430. doi: 10.3346/jkms.2014.29.3.423
54. Al-Rajhi A, Mardini L, Jayaraman D (2015) The Impact of Implementation of an ICU Consult Service on Hospital-Wide Outcomes and ICU-Specific Outcomes. J Intensive Care Med. doi: 10.1177/0885066615583794
55. Guirgis FW, Gerdik C, Wears RL, et al. (2013) Proactive rounding by the rapid response team reduces inpatient cardiac arrests. Resuscitation 84:1668–1673. doi: 10.1016/j.resuscitation.2013.08.013
56. McNeill G, Bryden D (2013) Do either early warning systems or emergency response teams improve hospital patient survival? A systematic review. Resuscitation 84:1652–1667. doi: 10.1016/j.resuscitation.2013.08.006
57. Kumar A, Roberts D, Wood KE, et al. (2006) Duration of hypotension before initiation of effective antimicrobial therapy is the critical determinant of survival in human septic shock. Crit Care Med 34:1589–1596. doi: 10.1097/01.CCM.0000217961.75225.E9
58. Beck V, Chateau D, Bryson GL, et al. (2014) Timing of vasopressor initiation and mortality in septic shock: a cohort study. Crit Care Lond Engl 18:R97. doi: 10.1186/cc13868
59. Lee SJ, Ramar K, Park JG, et al. (2014) Increased fluid administration in the first three hours of sepsis resuscitation is associated with reduced mortality: a retrospective cohort study. Chest 146:908–915. doi: 10.1378/chest.13-2702
60. Sandroni C, Caricato A (2013) Are rapid response systems effective in reducing hospital mortality? Crit Care Med 41:679–680. doi: 10.1097/CCM.0b013e318275cb7d
1
Acknowledgements
We thank the nurses and physicians of the rapid response team of the ICUof Saint Eloi hospital for their work in collecting data and their support in the MET implementation. The authors also acknowledge Valerie Maccioce for the english editing, David Demoulin for his invaluable help and support in extracting data from the hospital database and the Montpellier University Hospital communication department for having designed the MET flyers and poster.