Association of Opioids and Sedatives with Increased Risk of In-Hospital Cardiopulmonary Arrest from an Administrative Database

Frank J Overdyk, Oonagh Dowling, Joseph Marino, Jiejing Qiu, Hung-Lun Chien, Mary Erslon, Neil Morrison, Brooke Harrison, Albert Dahan, Tong J Gan, Frank J Overdyk, Oonagh Dowling, Joseph Marino, Jiejing Qiu, Hung-Lun Chien, Mary Erslon, Neil Morrison, Brooke Harrison, Albert Dahan, Tong J Gan

Abstract

Background: While opioid use confers a known risk for respiratory depression, the incremental risk of in-hospital cardiopulmonary arrest, respiratory arrest, or cardiopulmonary resuscitation (CPRA) has not been studied. Our aim was to investigate the prevalence, outcomes, and risk profile of in-hospital CPRA for patients receiving opioids and medications with central nervous system sedating side effects (sedatives).

Methods: A retrospective analysis of adult inpatient discharges from 2008-2012 reported in the Premier Database. Patients were grouped into four mutually exclusive categories: (1) opioids and sedatives, (2) opioids only, (3) sedatives only, and (4) neither opioids nor sedatives.

Results: Among 21,276,691 inpatient discharges, 53% received opioids with or without sedatives. A total of 96,554 patients suffered CPRA (0.92 per 1000 hospital bed-days). Patients who received opioids and sedatives had an adjusted odds ratio for CPRA of 3.47 (95% CI: 3.40-3.54; p<0.0001) compared with patients not receiving opioids or sedatives. Opioids alone and sedatives alone were associated with a 1.81-fold and a 1.82-fold (p<0.0001 for both) increase in the odds of CPRA, respectively. In opioid patients, locations of CPRA were intensive care (54%), general care floor (25%), and stepdown units (15%). Only 42% of patients survived CPRA and only 22% were discharged home. Opioid patients with CPRA had mean increased hospital lengths of stay of 7.57 days and mean increased total hospital costs of $27,569.

Conclusions: Opioids and sedatives are independent and additive risk factors for in-hospital CPRA. The impact of opioid sparing analgesia, reduced sedative use, and better monitoring on CPRA incidence deserves further study.

Conflict of interest statement

Competing Interests: This analysis was supported by Covidien Healthcare Economics and Outcomes Research. JQ, HLC, and ME are Covidien employees. FJO and JM are employed by North American Partners in Anesthesia. NM is employed by Harrier Consultancy. BH is employed by Boulder Medical Writing. FJO and TJG report grant support and honorarium from Covidien, unrelated to the submitted work. NM and BH report personal fees from Covidien during the conduct of the study. AD reports grants and personal fees from Mundipharma Int. Cambridge, UK; grants from Galleon Pharmaceuticals Corp. PA, USA; grants and personal fees from Revive Therapeutics, Ontario, Canada; grants and personal fees from Gruenenthal GmbH, Aachen, Germany; grants from Royal Dutch Shell, The Hague, Netherlands; grants and personal fees from MSD Netherlands, outside the submitted work. There are no patents, products in development, or marketed products to declare. This does not alter the authors' adherence to all the PLOS ONE policies on sharing data and materials.

Figures

Fig 1. Study Design and Patient Disposition.
Fig 1. Study Design and Patient Disposition.
The Premier Hospital Database was queried for eligible patients who received opioids, with or without medications with sedative properties, and had in-hospital cardiopulmonary or respiratory arrest or cardiopulmonary resuscitation (CPRA) as defined through ICD-9-CM and CPT codes.
Fig 2. Odds Ratios and Opioid Patient…
Fig 2. Odds Ratios and Opioid Patient Disposition.
(A) Adjusted Odds Ratio (95% CI) of cardiopulmonary or respiratory arrest or cardiopulmonary resuscitation (CPRA) by medication type. (B) Disposition (%) of opioid patients by location of arrest. The number of patients per category is shown within each bar. Facility: includes skilled nursing facility; intermediate care facility; hospice-medical facility; swing bed; another rehab facility; long-term care hospital; nursing facility; hospice-home; federal hospital or critical access hospital. CPA = cardiopulmonary arrest; CPR = cardiopulmonary resuscitation; GCF = general care floor; ICU = intensive care unit; RA = respiratory arrest.

References

    1. Kohn LT, Corrigan JM, Donaldson MS, editors. To err is human: building a safer health system: National Academy Press, Institute of Medicine; 1999
    1. Morrison LJ, Neumar RW, Zimmerman JL, Link MS, Newby LK, McMullan PW Jr., et al. Strategies for improving survival after in-hospital cardiac arrest in the United States: 2013 consensus recommendations: a consensus statement from the American Heart Association. Circulation. 2013;127(14):1538–63. 10.1161/CIR.0b013e31828b2770 .
    1. Girotra S, Nallamothu BK, Spertus JA, Li Y, Krumholz HM, Chan PS, et al. Trends in survival after in-hospital cardiac arrest. N Engl J Med. 2012;367(20):1912–20. 10.1056/NEJMoa1109148
    1. Ebell MH, Jang W, Shen Y, Geocadin RG, Get With the Guidelines-Resuscitation I. Development and validation of the Good Outcome Following Attempted Resuscitation (GO-FAR) score to predict neurologically intact survival after in-hospital cardiopulmonary resuscitation. JAMA Intern Med. 2013;173(20):1872–8. 10.1001/jamainternmed.2013.10037 .
    1. Hillman K, Chen J, Cretikos M, Bellomo R, Brown D, Doig G, et al. Introduction of the medical emergency team (MET) system: a cluster-randomised controlled trial. Lancet. 2005;365(9477):2091–7. 10.1016/S0140-6736(05)66733-5 .
    1. Chan PS, Khalid A, Longmore LS, Berg RA, Kosiborod M, Spertus JA. Hospital-wide code rates and mortality before and after implementation of a rapid response team. JAMA. 2008;300(21):2506–13. 10.1001/jama.2008.715 .
    1. Jarzyna D, Jungquist CR, Pasero C, Willens JS, Nisbet A, Oakes L, et al. American Society for Pain Management Nursing guidelines on monitoring for opioid-induced sedation and respiratory depression. Pain Manag Nurs. 2011;12(3):118–45 e10. 10.1016/j.pmn.2011.06.008 .
    1. Parsells Kelly J, Cook SF, Kaufman DW, Anderson T, Rosenberg L, Mitchell AA. Prevalence and characteristics of opioid use in the US adult population. Pain. 2008;138(3):507–13. 10.1016/j.pain.2008.01.027 .
    1. Sullivan MD, Edlund MJ, Fan MY, Devries A, Brennan Braden J, Martin BC. Trends in use of opioids for non-cancer pain conditions 2000–2005 in commercial and Medicaid insurance plans: the TROUP study. Pain. 2008;138(2):440–9. 10.1016/j.pain.2008.04.027
    1. Zerzan JT, Morden NE, Soumerai S, Ross-Degnan D, Roughead E, Zhang F, et al. Trends and geographic variation of opiate medication use in state Medicaid fee-for-service programs, 1996 to 2002. Med Care. 2006;44(11):1005–10. 10.1097/01.mlr.0000228025.04535.25 .
    1. Oderda GM, Said Q, Evans RS, Stoddard GJ, Lloyd J, Jackson K, et al. Opioid-related adverse drug events in surgical hospitalizations: impact on costs and length of stay. Ann Pharmacother. 2007;41(3):400–6. 10.1345/aph.1H386 .
    1. Davies EC, Green CF, Taylor S, Williamson PR, Mottram DR, Pirmohamed M. Adverse drug reactions in hospital in-patients: a prospective analysis of 3695 patient-episodes. PLoS One. 2009;4(2):e4439 10.1371/journal.pone.0004439
    1. Dahan A, Aarts L, Smith TW. Incidence, reversal, and prevention of opioid-induced respiratory depression. Anesthesiology. 2010;112(1):226–38. 10.1097/ALN.0b013e3181c38c25 .
    1. Oderda GM, Gan TJ, Johnson BH, Robinson SB. Effect of opioid-related adverse events on outcomes in selected surgical patients. J Pain Palliat Care Pharmacother. 2013;27(1):62–70. 10.3109/15360288.2012.751956 .
    1. The Joint Commission. Safe use of opioids in hospitals. Sentinel Event Alert 2012. .
    1. Lee LA, Caplan RA, Stephens LS, Posner KL, Terman GW, Voepel-Lewis T, et al. Postoperative opioid-induced respiratory depression: a closed claims analysis. Anesthesiology. 2015;122(3):659–65. 10.1097/ALN.0000000000000564 .
    1. Herzig SJ, Rothberg MB, Cheung M, Ngo LH, Marcantonio ER. Opioid utilization and opioid-related adverse events in nonsurgical patients in US hospitals. J Hosp Med. 2014;9(2):73–81. 10.1002/jhm.2102
    1. Bailey PL, Pace NL, Ashburn MA, Moll JW, East KA, Stanley TH. Frequent hypoxemia and apnea after sedation with midazolam and fentanyl. Anesthesiology. 1990;73(5):826–30. .
    1. Giummarra MJ, Gibson SJ, Allen AR, Pichler AS, Arnold CA. Polypharmacy and chronic pain: harm exposure is not all about the opioids. Pain Medicine. 2014.
    1. Howington JA, Gunnarsson CL, Maddaus MA, McKenna RJ, Meyers BF, Miller D, et al. In-hospital clinical and economic consequences of pulmonary wedge resections for cancer using video-assisted thoracoscopic techniques vs traditional open resections: a retrospective database analysis. Chest. 2012;141(2):429–35. 10.1378/chest.10-3013 .
    1. Lindenauer PK, Pekow P, Wang K, Mamidi DK, Gutierrez B, Benjamin EM. Perioperative beta-blocker therapy and mortality after major noncardiac surgery. N Engl J Med. 2005;353(4):349–61. 10.1056/NEJMoa041895 .
    1. Lindenauer PK, Stefan MS, Shieh MS, Pekow PS, Rothberg MB, Hill NS. Outcomes associated with invasive and noninvasive ventilation among patients hospitalized with exacerbations of chronic obstructive pulmonary disease. JAMA Intern Med. 2014;174(12):1982–93. 10.1001/jamainternmed.2014.5430 .
    1. Merchant RM, Yang L, Becker LB, Berg RA, Nadkarni V, Nichol G, et al. Incidence of treated cardiac arrest in hospitalized patients in the United States. Crit Care Med. 2011;39(11):2401–6. 10.1097/CCM.0b013e3182257459
    1. Peberdy MA, Kaye W, Ornato JP, Larkin GL, Nadkarni V, Mancini ME, et al. Cardiopulmonary resuscitation of adults in the hospital: a report of 14720 cardiac arrests from the National Registry of Cardiopulmonary Resuscitation. Resuscitation. 2003;58(3):297–308. .
    1. Ehlenbach WJ, Barnato AE, Curtis JR, Kreuter W, Koepsell TD, Deyo RA, et al. Epidemiologic study of in-hospital cardiopulmonary resuscitation in the elderly. N Engl J Med. 2009;361(1):22–31. 10.1056/NEJMoa0810245
    1. Sandroni C, Nolan J, Cavallaro F, Antonelli M. In-hospital cardiac arrest: incidence, prognosis and possible measures to improve survival. Intensive Care Med. 2007;33(2):237–45. 10.1007/s00134-006-0326-z .
    1. Larkin GL, Copes WS, Nathanson BH, Kaye W. Pre-resuscitation factors associated with mortality in 49,130 cases of in-hospital cardiac arrest: a report from the National Registry for Cardiopulmonary Resuscitation. Resuscitation. 2010;81(3):302–11. 10.1016/j.resuscitation.2009.11.021 .
    1. Chan PS, Nichol G, Krumholz HM, Spertus JA, Jones PG, Peterson ED, et al. Racial differences in survival after in-hospital cardiac arrest. JAMA. 2009;302(11):1195–201. 10.1001/jama.2009.1340
    1. Reed K, May R. HealthGrades Patient Safety in American Hospitals Study. . 2011.
    1. Hillman KM, Bristow PJ, Chey T, Daffurn K, Jacques T, Norman SL, et al. Antecedents to hospital deaths. Intern Med J. 2001;31(6):343–8. .
    1. Chan PS, Jain R, Nallmothu BK, Berg RA, Sasson C. Rapid response teams: a systematic review and meta-analysis. Arch Intern Med. 2010;170(1):18–26. 10.1001/archinternmed.2009.424 .
    1. Galhotra S, DeVita MA, Simmons RL, Dew MA, Members of the Medical Emergency Response Improvement Team C. Mature rapid response system and potentially avoidable cardiopulmonary arrests in hospital. Qual Saf Health Care. 2007;16(4):260–5. 10.1136/qshc.2007.022210
    1. Devita MA, Bellomo R, Hillman K, Kellum J, Rotondi A, Teres D, et al. Findings of the first consensus conference on medical emergency teams. Crit Care Med. 2006;34(9):2463–78. 10.1097/01.CCM.0000235743.38172.6E .
    1. Sun Z, Sessler DI, Dalton JE, Devereaux PJ, Shahinyan A, Naylor AJ, et al. Postoperative hypoxemia is common and persistent: a prospective blinded observational study. Anesth Analg. 2015;121(3):709–15. 10.1213/ANE.0000000000000836 .
    1. Chen J, Hillman K, Bellomo R, Flabouris A, Finfer S, Cretikos M, et al. The impact of introducing medical emergency team system on the documentations of vital signs. Resuscitation. 2009;80(1):35–43. 10.1016/j.resuscitation.2008.10.009 .
    1. Taenzer AH, Pyke JB, McGrath SP, Blike GT. Impact of pulse oximetry surveillance on rescue events and intensive care unit transfers: a before-and-after concurrence study. Anesthesiology. 2010;112(2):282–7. 10.1097/ALN.0b013e3181ca7a9b .
    1. .
    1. Peberdy MA, Callaway CW, Neumar RW, Geocadin RG, Zimmerman JL, Donnino M, et al. Part 9: post-cardiac arrest care: 2010 American Heart Association Guidelines for Cardiopulmonary Resuscitation and Emergency Cardiovascular Care. Circulation. 2010;122(18 Suppl 3):S768–86. 10.1161/CIRCULATIONAHA.110.971002 .

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