Effects of prolonged controlled mechanical ventilation on diaphragmatic function in healthy adult baboons

Anzueto, Antonio; Peters, Jay I.; Tobin, Martin J.; Santos, R. de los; Seidenfeld, John J.; Moore, Gary; Cox, Wesley J.; Coalson, Jacqueline J.

doi:10.1097/00003246-199707000-00021

Cited by 167 publications

(129 citation statements)

References 15 publications

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“…This original account was quickly supported by another study depicting the influence of prolonged MV on in vivo diaphragm function in healthy baboons (6). This primate study concluded that prolonged MV results in significant impairment of diaphragmatic contractile performance as indicated by a decrease in both maximal transdiaphragmatic pressure and diaphragmatic endurance (6). Following these early investigations, scientific interest in the effects of MV on diaphragm structure and function grew rapidly, and numerous animal studies published in 2002-2003 consistently concluded that prolonged MV results in the rapid development of both diaphragmatic atrophy and contractile dysfunction (16,19,33,91,93,98,100).…”

Section: Ventilator-induced Diaphragm Dysfunction: Historical Overviewmentioning

confidence: 87%

“…This landmark research revealed that 48 h of controlled MV (i.e., full ventilator support of breathing) resulted in significant loss of diaphragm mass and a large reduction in maximal diaphragmatic specific force production. This original account was quickly supported by another study depicting the influence of prolonged MV on in vivo diaphragm function in healthy baboons (6). This primate study concluded that prolonged MV results in significant impairment of diaphragmatic contractile performance as indicated by a decrease in both maximal transdiaphragmatic pressure and diaphragmatic endurance (6).…”

Section: Ventilator-induced Diaphragm Dysfunction: Historical Overviewmentioning

confidence: 94%

“…MECHANICAL VENTILATION AND DIAPHRAGM that 11 days of full support MV combined with neuromuscular blockade resulted in impaired diaphragmatic fatigue in healthy baboons (6). In contrast, 18 h of full support MV in rats has been shown to improve diaphragmatic endurance measured in vitro (98).…”

Section: R470mentioning

confidence: 99%

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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: Ventilator-induced Diaphragm Dysfunction: Historical Overviewmentioning

confidence: 87%

Section: Ventilator-induced Diaphragm Dysfunction: Historical Overviewmentioning

confidence: 94%

See 1 more Smart Citation

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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“…is characterized by a reduction in diaphragm force generation capacity due to controlled mechanical ventilation (CMV) and was recently shown to occur in humans 1 , being well-recognized in animal models as well, like rats 2,3 , rabbits 4 , piglets 5 , and baboons 6 .…”

Section: Ventilator-induced Diaphragmatic Dysfunction (Vidd)mentioning

confidence: 99%

“…Animals did not receive anesthetic doses in a continuous form or neuromuscular blockers, like in other studies 6,10 . Barbiturates and neuromuscular blockers have deleterious effects in skeletal muscle function 29 .…”

Section: Analysis Of Experimental Designmentioning

confidence: 99%

Effects of controlled and pressure support mechanical ventilation on rat diaphragm muscle

Oliveira

Costa²,

Assis

et al. 2012

Acta Cir. Bras.

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PURPOSE:The objective of this study was to analyze the effects of Pressure Controlled Ventilation mode (PCV-C) and PSV mode in diaphragm muscle of rats. METHODS: Wistar rats (n=18) were randomly assigned to the control group or to receive 6 hours of PCV and PSV. After this period, animals were euthanized and their diaphragms were excised, frozen in liquid nitrogen and stored in at -80º C for further histomorphometric analysis. RESULTS: Results showed a 15% decrease in cross-sectional area of muscle fibers on the PCV-C group when compared to the control group (p<0.001) and by 10% when compared to the PSV group (p<0.05). Minor diameter was decreased in PCV-C group by 9% when compared with the control group (p<0.001) and by 6% when compared to the PSV group (p<0.05). When myonuclear area was analyzed, a 16% decrease was observed in the PCV-C group when compared to the PSV group (p<0.05). No significant difference between the groups was observed in myonuclear perimeter (p>0.05). CONCLUSION: Short-term controlled mechanical ventilation seems to lead to muscular atrophy in diaphragm fibers. The PSV mode may attenuate the effects of VIDD. Key words: Anatomy & Histology. Diaphragm. Tracheostomy. Rats, Wistar. RESUMO OBJETIVO:Avaliar os efeitos do modo ventilatório controlado por pressão controlada (PCV-C) e do modo PSV sobre o músculo diafragma de ratos. MÉTODOS: Ratos (n = 18) da linhagem Wistar foram distribuídos no grupo controle (RE) ou para receber AVM por 6 horas no modo PCV-C e no modo PSV. Após esse período, os animais foram eutanasiados, o diafragma retirado e encaminhado para a análise histológica e morfométrica. RESULTADOS: Os resultados revelaram uma redução da área das fibras musculares de 15% no grupo PCV-C em comparação ao controle (p<0,001) e de 10% quando comparado ao grupo PSV (p<0,05). Já com relação ao diâmetro menor observou-se uma redução de 9% do grupo PCV-C em comparação ao controle (p<0,001) e de 6% em relação ao grupo PSV (p<0,05). Quando avaliada a área dos mionúcleos, notou-se uma redução de 16% desse parâmetro no grupo PCV-C, comparado ao PSV (p<0,05). Não houve diferença significativa no perímetro dos mionúcleos entre os grupos estudados (p>0,05). CONCLUSÃO: O grupo PCV-C apresentou atrofia muscular em um período curto de ventilação mecânica. O modo PSV parece atenuar os efeitos da DDIV.

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Ventilatory Failure, Ventilator Support, and Ventilator Weaning

Tobin

Laghi

Jubran

2012

Comprehensive Physiology

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The development of acute ventilatory failure represents an inability of the respiratory control system to maintain a level of respiratory motor output to cope with the metabolic demands of the body. The level of respiratory motor output is also the main determinant of the degree of respiratory distress experienced by such patients. As ventilatory failure progresses and patient distress increases, mechanical ventilation is instituted to help the respiratory muscles cope with the heightened workload. While a patient is connected to a ventilator, a physician's ability to align the rhythm of the machine with the rhythm of the patient's respiratory centers becomes the primary determinant of the level of rest accorded to the respiratory muscles. Problems of alignment are manifested as failure to trigger, double triggering, an inflationary gas-flow that fails to match inspiratory demands, and an inflation phase that persists after a patient's respiratory centers have switched to expiration. With recovery from disorders that precipitated the initial bout of acute ventilatory failure, attempts are made to discontinue the ventilator (weaning). About 20% of weaning attempts fail, ultimately, because the respiratory controller is unable to sustain ventilation and this failure is signaled by development of rapid shallow breathing. Substantial advances in the medical management of acute ventilatory failure that requires ventilator assistance are most likely to result from research yielding novel insights into the operation of the respiratory control system.

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Effects of prolonged controlled mechanical ventilation on diaphragmatic function in healthy adult baboons

Cited by 167 publications

References 15 publications

Ventilator-induced diaphragm dysfunction: cause and effect

Ventilator-induced diaphragm dysfunction: cause and effect

Effects of controlled and pressure support mechanical ventilation on rat diaphragm muscle

Ventilatory Failure, Ventilator Support, and Ventilator Weaning

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