Sedation, analgesia, and neuromuscular blockade in sepsis: An evidence-based review

Vender, Jeffery S.; Szokol, Joseph W.; Murphy, Glenn S.; Nitsun, Martin

doi:10.1097/01.ccm.0000145907.86298.12

Cited by 66 publications

(31 citation statements)

References 81 publications

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“…Neuromuscular blocking agents are still being used, although much less frequently and more selectively to date, for several indications such as urgent intubation, patient-ventilator asynchrony, refractory respiratory failure, intracranial hypertension, and therapeutic hypothermia (265). Despite the lack of equivocal evidence of negative neuromuscular effects, it is generally accepted to limit use of neuromuscular blocking agents (146) and when used, to evaluate depth of neuromuscular blockade applying monitoring techniques (744).…”

Section: F Management Of Neuromuscular Blockadementioning

confidence: 99%

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

Friedrich

Reid

Berghe

et al. 2015

Physiological Reviews

300

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: F Management Of Neuromuscular Blockadementioning

confidence: 99%

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

Friedrich

Reid

Berghe

et al. 2015

Physiological Reviews

300

329

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“…Furthermore, ICU-acquired weakness is associated with increased ICU stay, increased hospital stay, and also increased mortality. [6][7][8] Therefore, guidelines regarding the use of NMBAs in the ICU typically caution that they should be limited to refractory hypoxemia and hypercarbia, and they should be short-term and guided by train-of-four monitoring. 9 Despite suggestions that NMBAs negatively affect both morbidity and mortality in critically ill patients, there has been a paucity of confirmatory data from randomized trials.…”

Section: Commentarymentioning

confidence: 99%

The role of neuromuscular blocking drugs in early severe acute respiratory distress syndrome

Needham

Brindley

2011

Can J Anesth/J Can Anesth

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Background Acute respiratory distress syndrome (ARDS) is defined as severe hypoxemic respiratory failure resulting from diffuse lung injury and secondary to direct and indirect insults. Despite advances, mortality remains as high as 40-60%. Neuromuscular blocking agents (NMBAs) are used to facilitate mechanical ventilation in patients with ARDS and have been shown to improve arterial partial pressure of oxygen. However, the association between NMBAs and mortality is unclear. Furthermore, morbidity concerns exist, particularly regarding a putative role in intensive care unit (ICU)-acquired weakness. Objective The purpose of this study was to compare survival in adult patients with early ARDS who were randomized to receive either a 48-hr infusion of the NMBA, cisatracurium, or a placebo. Patients Eligible patients were [ 18 yr with an intubated trachea and ventilated lungs for acute hypoxemic respiratory failure. Their PaO 2 /F I O 2 ratio was \ 150 at a tidal volume of 6-8 mLÁkg -1 ideal body weight and a positive end-expiratory pressure (PEEP) C 5 cm H 2 O for \ 48 hr. Additional inclusion criteria were radiographic evidence of bilateral pulmonary infiltrates and the absence of left atrial hypertension. Exclusion criteria included patients already receiving NMBA at enrolment; those who had increased intracranial pressure, severe chronic respiratory disease, or severe chronic liver disease; those who had received a bone marrow transplant or had chemotherapy-induced neutropenia; those who had a pneumothorax; and those who were expected to require mechanical ventilation for \ 48 hr or were enrolled in another trial within 30 days. Intervention Three hundred twenty-six patients were screened, and 340 of these underwent randomization in blocks of four and received either a 48-hr infusion of cisatracurium (15 mg bolus followed by 37.5 mgÁhr -1 ) or a volume equivalent placebo. One hundred and seventy-eight patients received a cisatracurium infusion, and one patient withdrew leaving 177 patients included in the analysis. One hundred and sixty-two patients received the placebo infusion. Prior to either infusion, patients were sedated to a Ramsay sedation score of 6. Patients' lungs were ventilated by a volume assist-controlled mode according to the ARDS Clinical Network Mechanical Ventilation Protocol (http:// www.ardsnet.org/) with the goal SpO 2 of 88-95% (or PaO 2 55-80 mmHg) and goal plateau pressure B 35 cm H 2 O. Open-label boluses of cisatracurium 20 mg (maximum of two per 24-hr period) were allowed if plateau pressures Design and setting

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“…However, the use of benzylisoquinoline NMBAs has also been associated with this adverse event. 79,96,97 In considering recovery of neuromuscular function after discontinuation of NMBAs, the benzylisoquinoline class may be advantageous, due to their lack of dependence on end-organ metabolism, especially in critically ill patients with impaired hepatic and/or renal function. 96,98 It is worth noting that short-term infusion of cisatracurium (48 h) was used in all 3 of the recent randomized controlled trials demonstrating an improvement in outcomes in critically ill patients with early phase ARDS.…”

Section: Choice Of Nmbas and Monitoring Depth Of Paralysismentioning

confidence: 99%

“…95 At present, there are limited data to support the use of one NMBA over another in critically ill patients. 76,96 Due to its low cost and long duration of action, pancuronium has been the recommended drug for pharmacologic paralysis in critically ill patients, except in those patients where the vagolytic effect of this agent might be detrimental. 76,96 Similarities in the structure of aminosteroid NMBAs and corticosteroids have raised concern in the past for an increased incidence of ICU-acquired weakness after prolonged administration.…”

Section: Choice Of Nmbas and Monitoring Depth Of Paralysismentioning

confidence: 99%

Sedation and ParalysisDiscussion

et al. 2013

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Sedation is used almost universally in the care of critically ill patients, especially in those who require mechanical ventilatory support or other life-saving invasive procedures. This review will focus on the sedation strategies for critically ill patients and the pharmacology of commonly used sedative agents. The role of neuromuscular blocking agents in the ICU will be examined and the pharmacology of commonly used agents is reviewed. Finally a strategy for rational use of these sedative and neuromuscular blocking agents in critically ill patients will be proposed.

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Sedation, analgesia, and neuromuscular blockade in sepsis: An evidence-based review

Cited by 66 publications

References 81 publications

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

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

The role of neuromuscular blocking drugs in early severe acute respiratory distress syndrome

Sedation and ParalysisDiscussion

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