Opioids and Infections in the Intensive Care Unit Should Clinicians and Patients be Concerned?

Weinert, Craig R.; Kethireddy, Shravan; Roy, Sabita

doi:10.1007/s11481-008-9124-4

Cited by 19 publications

(9 citation statements)

References 104 publications

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“…Indeed, available evidence indicates that opioids have immunosuppressive effects and are capable of increasing mortality in animal models of infection [27,56]. Additionally, fentanyl may contribute to delirium [6].…”

Section: Discussionmentioning

confidence: 99%

Effect of dexmedetomidine versus lorazepam on outcome in patients with sepsis: an a priori-designed analysis of the MENDS randomized controlled trial

et al. 2010

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IntroductionBenzodiazepines and α2 adrenoceptor agonists exert opposing effects on innate immunity and mortality in animal models of infection. We hypothesized that sedation with dexmedetomidine (an α2 adrenoceptor agonist), as compared with lorazepam (a benzodiazepine), would provide greater improvements in clinical outcomes among septic patients than among non-septic patients.MethodsIn this a priori-determined subgroup analysis of septic vs non-septic patients from the MENDS double-blind randomized controlled trial, adult medical/surgical mechanically ventilated patients were randomized to receive dexmedetomidine-based or lorazepam-based sedation for up to 5 days. Delirium and other clinical outcomes were analyzed comparing sedation groups, adjusting for clinically relevant covariates as well as assessing interactions between sedation group and sepsis.ResultsOf the 103 patients randomized, 63 (31 dexmedetomidine; 32 lorazepam) were admitted with sepsis and 40 (21 dexmedetomidine; 19 lorazepam) without sepsis. Baseline characteristics were similar between treatment groups for both septic and non-septic patients. Compared with septic patients who received lorazepam, the dexmedetomidine septic patients had 3.2 more delirium/coma-free days (DCFD) on average (95% CI for difference, 1.1 to 4.9), 1.5 (-0.1, 2.8) more delirium-free days (DFD) and 6 (0.3, 11.1) more ventilator-free days (VFD). The beneficial effects of dexmedetomidine were more pronounced in septic patients than in non-septic patients for both DCFDs and VFDs (P-value for interaction = 0.09 and 0.02 respectively). Additionally, sedation with dexmedetomidine, compared with lorazepam, reduced the daily risk of delirium [OR, CI 0.3 (0.1, 0.7)] in both septic and non-septic patients (P-value for interaction = 0.94). Risk of dying at 28 days was reduced by 70% [hazard ratio 0.3 (0.1, 0.9)] in dexmedetomidine patients with sepsis as compared to the lorazepam patients; this reduction in death was not seen in non-septic patients (P-value for interaction = 0.11).ConclusionsIn this subgroup analysis, septic patients receiving dexmedetomidine had more days free of brain dysfunction and mechanical ventilation and were less likely to die than those that received a lorazepam-based sedation regimen. These results were more pronounced in septic patients than in non-septic patients. Prospective clinical studies and further preclinical mechanistic studies are needed to confirm these results.Trial RegistrationNCT00095251.

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Section: Discussionmentioning

confidence: 99%

Effect of dexmedetomidine versus lorazepam on outcome in patients with sepsis: an a priori-designed analysis of the MENDS randomized controlled trial

et al. 2010

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“…The Society of Critical Care Medicine advocates the use of morphine as the drug of choice for pain management in mechanically ventilated patients [3]. A systematic review of 43 studies analyzing the use of opioids in patients in the intensive care unit concluded that the median morphine dose was 0.7 mg/kg/day or approximately 49mg/day in a 70kg patient [4]. However, opioids are known to cause respiratory depression and subsequent cardiopulmonary arrests.…”

Section: Introductionmentioning

confidence: 99%

Respiratory Effects of Opioids in Perioperative Medicine

Koo¹,

Eikermann

2011

TOATJ

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Opioids are widely used to treat acute and chronic pain as well as respiratory distress. There is great variability in opioid-induced side effects due to individual biological factors, patient co-morbidities and drug interactions. Normal respiratory rhythm generation is decreased primarily via inhibititory effects within the pre-Bötzinger complex. Central chemosensitivity to hypercapnia and hypoxia are blunted by opioids at the levels of the retrotrapezoid nucleus, medullary raphe nucles and nucleus tractus solitarius. Opioids also decrease central drive to both respiratory pump muscles and the upper airway dilator muscles. Opioid-induced respiratory depression can be reversed by naloxone, and recent data suggest that 5-HT4(a) agonists and ampakines are effective to reverse some of the opioid-induced respiratory depressant effects. The potentially fatal side effects of respiratory depression within the acute peri-operative setting necessitates effective monitoring of respiratory function in all patients receiving opioid therapy. Each institution needs to develop an optimal organization structure locally to define appropriate methods for avoiding medication errors, titrating opioids to target effect, and monitoring for respiratory side effects.

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“…2,3 They are potent analgesics, have few clinically apparent adverse effects on other organ systems, and have consistent pharmacokinetics. 4 Opioids are naturally occurring alkaloids, related synthetic/semisynthetic compounds, and endogenous opioid peptides (enkephalins, endorphins, and dynorphins). 5 The exact physiologic function of endogenous opioids includes modulation of stress-induced analgesia and neurotransmitter, neuromodulator, and neurohormonal activity.…”

Section: Introductionmentioning

confidence: 99%