Rocuronium exacerbates mechanical ventilation–induced diaphragm dysfunction in rats

Testelmans, Dries; Maes, Karen; Wouters, Patrick; Gosselin, Nadège; DeRuisseau, Keith C.; Powers, Scott K.; Sciot, Raf; Decramer, Marc; Gayan‐Ramirez, Ghislaine

doi:10.1097/01.ccm.0000245783.28478.ad

Cited by 90 publications

(66 citation statements)

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“…A possible complication of using neuromuscular-blocking agents in the ICU is skeletal muscle myopathy and contractile dysfunction. In this regard, two investigations reveal that use of the neuromuscular-blocking agent rocuronium increases the magnitude of MV-induced diaphragmatic contractile dysfunction in rats (108,109). In contrast, another recent study using a porcine model of MV concluded that treatment of animals with rocuronium does not have an additive effect on MVinduced diaphragm dysfunction (78).…”

Section: Impact Of Age and Drugs On Mv-induced Diaphragmatic Contractmentioning

confidence: 97%

Ventilator-induced diaphragm dysfunction: cause and effect

Powers

Wiggs

Sollanek

et al. 2013

American Journal of Physiology-Regulatory, Integrative and Comp

143

156

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Powers SK, Wiggs MP, Sollanek KJ, Smuder AJ. Ventilator-induced diaphragm dysfunction: cause and effect. Am J Physiol Regul Integr Comp Physiol 305: R464 -R477, 2013. First published July 10, 2013 doi:10.1152/ajpregu.00231.2013 is used clinically to maintain gas exchange in patients that require assistance in maintaining adequate alveolar ventilation. Common indications for MV include respiratory failure, heart failure, drug overdose, and surgery. Although MV can be a life-saving intervention for patients suffering from respiratory failure, prolonged MV can promote diaphragmatic atrophy and contractile dysfunction, which is referred to as ventilator-induced diaphragm dysfunction (VIDD). This is significant because VIDD is thought to contribute to problems in weaning patients from the ventilator. Extended time on the ventilator increases health care costs and greatly increases patient morbidity and mortality. Research reveals that only 18 -24 h of MV is sufficient to develop VIDD in both laboratory animals and humans. Studies using animal models reveal that MV-induced diaphragmatic atrophy occurs due to increased diaphragmatic protein breakdown and decreased protein synthesis. Recent investigations have identified calpain, caspase-3, autophagy, and the ubiquitin-proteasome system as key proteases that participate in MV-induced diaphragmatic proteolysis. The challenge for the future is to define the MV-induced signaling pathways that promote the loss of diaphragm protein and depress diaphragm contractility. Indeed, forthcoming studies that delineate the signaling mechanisms responsible for VIDD will provide the knowledge necessary for the development of a pharmacological approach that can prevent VIDD and reduce the incidence of weaning problems. respiratory muscle; atrophy; mechanical ventilation; weaning; muscle wasting MECHANICAL VENTILATION (MV) is used clinically to achieve sufficient pulmonary gas exchange in patients unable to sustain adequate alveolar ventilation on their own. Common indications for MV include respiratory failure due to chronic obstructive pulmonary disease, status asthmaticus, and/or heart failure. In addition, MV is often an essential intervention in patients suffering from acute drug overdose, neuromuscular diseases, sepsis, and during surgery along with postsurgical recovery.The number of patients receiving prolonged MV in the United States exceeds more than 300,000 each year in the intensive care unit (ICU) (20). Although MV can be a lifesaving measure, prolonged MV results in the rapid development of diaphragmatic weakness due to both atrophy and contractile dysfunction. This detrimental impact of prolonged MV on the diaphragm has been termed ventilator-induced diaphragmatic dysfunction (VIDD) and VIDD is predicted to be a major contributor to problems in weaning patients from the ventilator (26, 114). Although previous reports describing the impact of prolonged MV on the diaphragm have appeared in the literature, advances in our understanding of the mechanisms responsible for VIDD h...

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Section: Impact Of Age and Drugs On Mv-induced Diaphragmatic Contractmentioning

confidence: 97%

Ventilator-induced diaphragm dysfunction: cause and effect

Powers

Wiggs

Sollanek

et al. 2013

American Journal of Physiology-Regulatory, Integrative and Comp

143

156

View full text Add to dashboard Cite

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“…For example, only a single benzylisoquinoline NMBA was used (cisatracurium), whereas steroidal agents (i.e., vecuronium, rocuronium, pancuronium) might lead to higher incidences of myopathy. 12 Moreover, NMBAs were used only early in ARDS and for only 48 hr-a period that may be too brief for ICUparesis. Post hoc analysis established that benefits were seen only in the two-thirds of patients with very severe disease (PaO2/FiO2 [P/F] ratio \ 120).…”

Section: Analysis Of Methodologymentioning

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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“…42 NBDs have been defined as a risk factor for critical illness polyneuropathy and myopathy, conditions manifested by muscle weakness in critically ill patients. [11][12][13][14]42 Moreover, infusion of rocuronium 12 and cisatracurium 14 for a single day in rats compromises diaphragmatic function by a myopathic mechanism that does not involve neuromuscular transmission failure. 12 Moreover, the combination of 18 to 69 hours of complete diaphragmatic inactivity and mechanical ventilation results in marked atrophy of myofibers in the diaphragm of humans.…”

Section: Discussionmentioning

confidence: 99%

“…[8][9][10] Moreover, long-term administration of NBDs is a risk factor for the development of critical illness polyneuropathy. [11][12][13][14] Finally, recent animal data suggest that a constant neuromuscular blockade with rocuronium and cisatracurium over only a single day evokes a myopathy that significantly decreases diaphragmatic force. 12,14 Therefore, we feel it is important for clinicians to get information about variables that predict the duration of action of NBDs administered long-term.…”

mentioning

confidence: 99%

“…[11][12][13][14] Finally, recent animal data suggest that a constant neuromuscular blockade with rocuronium and cisatracurium over only a single day evokes a myopathy that significantly decreases diaphragmatic force. 12,14 Therefore, we feel it is important for clinicians to get information about variables that predict the duration of action of NBDs administered long-term. We aimed at determining predictors of duration of action of cisatracurium and rocuronium administered long-term.…”

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confidence: 99%

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Clinical Predictors of Duration of Action of Cisatracurium and Rocuronium Administered Long-Term

Faßbender

Geldner

Blobner

et al. 2009

American Journal of Critical Care

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BackgroundThe duration of action of neuromuscular blocking drugs (NBDs) varies between individuals and even within individuals in different settings. Objectives To define predictors of variance in duration of action of rocuronium and cisatracurium administered long-term. Methods A prospective, double-blind, multicenter trial that included 113 patients scheduled for major abdominal surgery and postoperative admission to the intensive care unit. Patients received repetitive (median, 7) equipotent doses of rocuronium or cisatracurium to maintain deep relaxation (twitch height of the adductor pollicis muscle <25% of baseline). Effects of weight, age, sex, American Society of Anesthesiologists risk score, lowest core temperature, duration of NBD administration, and tobacco smoking history on duration of action of cisatracurium and rocuronium were determined via multiple regression analysis. Results Only duration of NBD administration was predictive of the duration of action of rocuronium. The predicted increase in time to recovery of the train-of-4 ratio to 0.9 (duration TOF 0.9) per hour of continuous NBD treatment was 12.4 minutes. In contrast, only lowest core body temperature was predictive of cisatracurium's duration of action, and the predicted in crease in duration TOF 0.9 per degree Celsius decrease was 9.8 min. Conclusion Duration of NBD treatment is strongly predictive of the duration of action of rocuronium, and body temperature is predictive of the duration of action of cisatracurium. These data may help decrease the incidence of drug-induced muscle weakness in recovery rooms and surgical intensive care units, particularly if neuromuscular transmission monitoring is not available.

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Rocuronium exacerbates mechanical ventilation–induced diaphragm dysfunction in rats

Cited by 90 publications

References 38 publications

Ventilator-induced diaphragm dysfunction: cause and effect

Ventilator-induced diaphragm dysfunction: cause and effect

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

Clinical Predictors of Duration of Action of Cisatracurium and Rocuronium Administered Long-Term

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