Efficacy and Safety of Analgosedation with Fentanyl Compared with Traditional Sedation with Propofol

Tedders, Kristen M.; McNorton, Kelly; Edwin, Stephanie B.

doi:10.1002/phar.1429

Cited by 20 publications

(14 citation statements)

References 22 publications

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“…Another error variable may stem from the fact that most studies on septic patients do not give further details whether and how patients were subjected to analgosedation (i.e., use of fentanyl or related analgo-sedatives to maintain intubation; Ref. 695) and mechanical ventilation and silencing that could further contribute to pro-inflammatory cytokine production. Since interstitial TNF-␣ concentrations might be substantially higher in LPS-stimulated muscle (known to additionally secrete TNF-␣; Ref.…”

Section: (196) (Figure 6)mentioning

confidence: 99%

The Sick and the Weak: Neuropathies/Myopathies in the Critically Ill

Friedrich

Reid

Berghe

et al. 2015

Physiological Reviews

291

329

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Critical illness polyneuropathies (CIP) and myopathies (CIM) are common complications of critical illness. Several weakness syndromes are summarized under the term intensive care unit-acquired weakness (ICUAW). We propose a classification of different ICUAW forms (CIM, CIP, sepsis-induced, steroid-denervation myopathy) and pathophysiological mechanisms from clinical and animal model data. Triggers include sepsis, mechanical ventilation, muscle unloading, steroid treatment, or denervation. Some ICUAW forms require stringent diagnostic features; CIM is marked by membrane hypoexcitability, severe atrophy, preferential myosin loss, ultrastructural alterations, and inadequate autophagy activation while myopathies in pure sepsis do not reproduce marked myosin loss. Reduced membrane excitability results from depolarization and ion channel dysfunction. Mitochondrial dysfunction contributes to energy-dependent processes. Ubiquitin proteasome and calpain activation trigger muscle proteolysis and atrophy while protein synthesis is impaired. Myosin loss is more pronounced than actin loss in CIM. Protein quality control is altered by inadequate autophagy. Ca 2ϩ dysregulation is present through altered Ca 2ϩ homeostasis. We highlight clinical hallmarks, trigger factors, and potential mechanisms from human studies and animal models that allow separation of risk factors that may trigger distinct mechanisms contributing to weakness. During critical illness, altered inflammatory (cytokines) and metabolic pathways deteriorate muscle function. ICUAW prevention/treatment is limited, e.g., tight glycemic control, delaying nutrition, and early mobilization. Future challenges include identification of primary/secondary events during the time course of critical illness, the interplay between membrane excitability, bioenergetic failure and differential proteolysis, and finding new therapeutic targets by help of tailored animal models.

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Section: (196) (Figure 6)mentioning

confidence: 99%

The Sick and the Weak: Neuropathies/Myopathies in the Critically Ill

Friedrich

Reid

Berghe

et al. 2015

Physiological Reviews

291

329

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“…7 Few studies have evaluated the benefit of a fentanyl-based protocol on outcomes in mechanically ventilated critically ill patients. 8 The objective of this study was to evaluate the impact of an analgosedation protocol on duration of mechanical ventilation, ICU length of stay (LOS), sedation levels, and medication costs.…”

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confidence: 99%

Impact of an Analgesia-Based Sedation Protocol on Mechanically Ventilated Patients in a Medical Intensive Care Unit

Faust

Rajan

Sheperd

et al. 2016

Anesthesia &Amp; Analgesia

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BACKGROUND Recent attention to adverse effects of intensive care unit (ICU) sedation has led to the use of strategies that target a “lighter” depth of sedation. Among these strategies are “analgosedation” protocols, which prioritize pain management and preferentially use IV opioids before administration of continuously infused sedatives such as propofol or midazolam. We hypothesized that using an analgosedation protocol would result in a shorter duration of mechanical ventilation than a protocol with greater emphasis on IV sedatives METHODS We conducted a retrospective study comparing the duration of mechanical ventilation before and after implementation of an analgosedation protocol in a 24-bed medical ICU. Patients were aged 18 years or older and required mechanical ventilation where a light level of sedation was clinically appropriate. Exclusion criteria included a clinical need for deeper levels of sedation or tracheal intubation confined to the perioperative period. RESULTS Seventy-nine patients were included in the postimplementation group and 65 in the preimplementation group. After adjustment for baseline covariates, introduction of the 2013 analgosedation protocol was associated with a decreased duration of mechanical ventilation (−26.62 hours; 95% confidence interval, − 44.98 to −8.26, P = 0.005). Patients managed with the analgosedation protocol experienced a lighter level of sedation (median Richmond Agitation-Sedation Scale, −2.57 vs −1.25, P = 0.001) and improved pain management (median Critical-Care Pain Observation Tool score, 2.0 vs 1.5, P = 0.03). The use of continuously infused sedatives was reduced by 54.3% (92.3% vs 38.0%, P < 0.001). CONCLUSIONS Our findings suggest that implementation of an analgosedation protocol was associated with an overall lighter level of sedation, shorter mean ventilator duration, and a reduced use of continuous infusion sedatives. Further studies are needed to assess the impact of such protocols on ICU delirium.

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“…Because fentanyl is the most commonly used opioid in the ICU, especially for sedation and/or intubation, there is potential for its application in critically ill patients admitted to the ICU with haemodynamic shock who require high-dose catecholamines. 20 Moreover, because fentanyl also protects the lungs, it could benefit patients being ventilated mechanically, particularly those at risk of ventilator-induced lung injury or ventilator-aggravated lung injury. 46 In addition, fentanyl could be used as an adjuvant drug for myocardial protection during resuscitation from cardiac arrest because it does not impair the haemodynamic effects of adrenaline.…”

Section: Discussionmentioning

confidence: 99%

“…Gasometry was performed using an ABL555 blood gas analyser (Radiometer America, Westlake, OH, USA). Lung compliance and airway pressure were measured continuously and recorded from anesthesia workstation (Primus Dr€ ager) at baseline and at 5,10,15,20,25,30,40,50, 60, 90, 120, 150, 180, 210, 240, 300, 330 and 360 min. The pulmonary shunt and AaDO 2 were calculated using standard formulae 50 (Fig.…”

Section: Measurement and Sampling Time Pointsmentioning

confidence: 99%

“…16 Based on these findings and the fact that fentanyl is the opioid most commonly used in the intensive care unit (ICU), especially for sedation and/or intubation, many patients who suffer a cardiac arrest and need CPR are already likely to be receiving this opioid. 20 Therefore, it was hypothesized that a CPR dose of adrenaline may be an independent cause of myocardial dysfunction and that fentanyl could attenuate the injury induced by high doses of adrenaline. Thus, the aim of the present study was to evaluate the effects of fentanyl on the structure and function of myocardial tissue in pigs exposed to CPR doses of adrenaline.…”

Section: Introductionmentioning

confidence: 99%

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Myocardial protection induced by fentanyl in pigs exposed to high‐dose adrenaline

Luz¹,

Otsuki

Gonzalez³

et al. 2015

Clin Exp Pharma Physio

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The use of high doses of adrenaline is common in critical patients, especially during cardiac arrest. During these situations, myocardial dysfunction can be a result of multiple factors, including adrenaline use. In addition, opioids have been shown to have anti-arrhythmic and anti-ischemic mechanisms that may confer cardiac protection. This study aimed to evaluate the effects of fentanyl on myocardial function in pigs exposed to high-dose adrenaline. After institutional ethics committee approval, 26 pigs were randomly allocated to receive either 20 μg/kg fentanyl (n = 10; fentanyl group) administered 5 min before five doses of adrenaline (20 μg/kg), equivalent-volume saline (n = 10; saline group) using the same adrenaline dosing protocol, or neither fentanyl nor adrenaline (n = 6; sham group). The fentanyl group showed lower levels of troponin at the end of the sixth hour compared with the saline group (1.91 ± 1.47 vs 5.44 ± 5.35 ng/mL, P = 0.019). Transmission electron microscopy and immunohistochemistry also showed less myocardial injury in the fentanyl group. The conclusion was reached that fentanyl attenuates myocardial injury caused by high-dose adrenaline without blunting the hemodynamic effect of adrenaline.

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Efficacy and Safety of Analgosedation with Fentanyl Compared with Traditional Sedation with Propofol

Abstract: Analgosedation with fentanyl appears to be a safe and effective strategy to facilitate mechanical ventilation. This regimen does not appear to affect duration of mechanical ventilation when compared with propofol, but may allow for more optimal pain management in critically ill patients.

Cited by 20 publications

References 22 publications

The Sick and the Weak: Neuropathies/Myopathies in the Critically Ill

The Sick and the Weak: Neuropathies/Myopathies in the Critically Ill

Impact of an Analgesia-Based Sedation Protocol on Mechanically Ventilated Patients in a Medical Intensive Care Unit

Myocardial protection induced by fentanyl in pigs exposed to high‐dose adrenaline

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