Signs of critical illness polyneuropathy and myopathy can be seen early in the ICU course.

BACKGROUND: Critical illness polyneuropathy and myopathy (CIPNM) is recognized as a common condition that develops in the intensive care unit (ICU). It may lead to a prolonged hospital stay with subsequent increased ICU and hospital costs. Knowledge of predisposing factors is insufficient and the temporal pattern of CIPNM has not been well described earlier. This study investigated patients with critical illness in need of prolonged mechanical ventilation, describing comprehensively the time course of changes in muscle and nerve neurophysiology, histology and mitochondrial oxidative function. METHODS: Ten intensive care patients were investigated 4, 14 and 28 days after the start of mechanical ventilation. Laboratory tests, neurophysiological examination, muscle biopsies and clinical examinations were performed. Neurophysiological criteria for CIPNM were noted and measurements for mitochondrial content, mitochondrial respiratory enzymes and markers of oxidative stress were performed. RESULTS: While all patients showed pathologic changes in neurophysiologic measurements, only patients with sepsis and steroid treatment (5/5) fulfilled the CIPNM criteria. The presence of CIPNM did not affect the outcome, and the temporal pattern of CIPNM was not uniform. All CIP changes occurred early in ICU care, while myopathy changes appeared somewhat later. Citrate synthase was decreased between days 4 and 14, and mitochondrial superoxide dismutase was increased. CONCLUSION: With comprehensive examination over time, signs of CIPNM can be seen early in ICU course, and appear more likely to occur in patients with sepsis and corticosteroid treatment.

Bispectral index as a predictor of sedation depth during isoflurane or midazolam sedation in ICU patients.

Bispectral index (BIS) is used for monitoring anaesthetic depth with inhaled anaesthetic agents in the operating room but has not been evaluated as a monitor of sedation depth in the intensive care unit (ICU) setting with these agents. If BIS could predict sedation depth in ICU patients, patient disturbances could be reduced and oversedation avoided. Twenty ventilator-dependent ICU patients aged 27 to 80 years were randomised to sedation with isoflurane via the AnaConDa or intravenous midazolam. BIS (A-2000 XP, version 3.12), electromyogram activity (EMG) and Signal Quality Index were measured continuously. Hourly clinical evaluation of sedation depth according to Bloomsbury Sedation Score (Bloomsbury) was performed. The median BIS value during a 10-minute interval prior to the clinical evaluation at the bedside was compared with Bloomsbury. Nurses performing the clinical sedation scoring were blinded to the BIS values. End-tidal isoflurane concentration was measured and compared with Bloomsbury. Correlation was poor between BIS and Bloomsbury in both groups (Spearman's rho 0.012 in the isoflurane group and -0.057 in the midazolam group). Strong correlation was found between BIS and EMG (Spearman's rho 0.74). Significant correlation was found between end-tidal isoflurane concentration and Bloomsbury (Spearman's rho 0.47). In conclusion, BIS XP does not reliably predict sedation depth as measured by clinical evaluation in non-paralysed ICU patients sedated with isoflurane or midazolam. EMG contributes significantly to BIS values in isoflurane or midazolam sedated, non-paralysed ICU patients. End-tidal isoflurane concentration appeared to be a better indicator of clinical sedation depth than BIS.

Effect of prolonged mechanical ventilation on diaphragm muscle mitochondria in piglets.

BACKGROUND: Respiratory muscle weakness is a common problem in the intensive care unit and could be involved in difficulties in weaning from the ventilator after prolonged mechanical ventilation. Animal models have shown that mechanical ventilation itself impairs diaphragm muscle function. In this study we investigated whether diaphragm contractile impairment caused by mechanical ventilation and immobilization in piglets is associated with a derangement in diaphragm mitochondria. METHODS: Seven piglets received controlled mechanical ventilation during 5 days. A control group of eight piglets were anaesthetized and surgically manipulated in the same way, but were mechanically ventilated for 4-6 h. After mechanical ventilation, diaphragm muscle biopsies were taken for measurements of mitochondria content, mitochondrial respiratory enzymes and markers of oxidative stress. RESULTS: Diaphragm mitochondrial content, as assessed by citrate synthase activities and volume density, was not different between the control and ventilated piglets. Activity of complex IV of the mitochondrial respiratory chain decreased by 21% (P=0.02) when expressed per muscle weight and by 11% (P=0.03) when expressed per citrate synthase activity. There were no changes in the markers of oxidative stress between the two groups. CONCLUSION: Five days of mechanical ventilation and immobilization decreased the activity of complex IV of the mitochondrial respiratory chain in the diaphragm muscle of the piglets.

Changes in diaphragm structure following prolonged mechanical ventilation in piglets.

BACKGROUND: Prolonged mechanical ventilation and inactivity negatively affect muscle function. The mechanisms for this dysfunction are unclear and clinical studies of respiratory muscle are difficult to carry out. An animal model simulating the critical care environment was used to investigate the effects of 5 days' mechanical ventilation and diaphragm inactivity on diaphragm muscle morphology. METHODS: Twelve 2-4-month-old piglets weighing 23-30 kg were studied. Seven animals received controlled mechanical ventilation and sedation such that spontaneous breathing efforts were inhibited over 5 days. Five control animals were ventilated for only 4-6 h following surgical preparation. Diaphragm biopsies were obtained from the left costal region at the end of all experiments. RESULTS: Morphometric, morphologic, electron microscopic and enzyme histochemical examination of costal diaphragm biopsies was carried out. Contractile properties were studied over 5 days and the results have been previously reported. Cross-sectional area of alI fiber types was increased compared with controls. The proportion of type IIb/x fibers increased following inactivity (P < 0,05) and the proportion of type I and IIa fibers tended to decrease although not significantly. Focal areas of diaphragm fiber regeneration were found without signs of inflammation. Increased appearance of cytoplasmic vacuoles consisting of lipid accumulation was noted in type I fibers. Several study animals developed focal areas with weak myofibrillar ATPase activity and disrupted fiber organization. There were areas of myofibrillary destruction and loss of sarcomeric pattern, without evidence of selective thick filament loss or a change in the myosin to actin ratio. CONCLUSION: Five days' mechanical ventilation with sedation and complete diaphragm inactivity resulted in changes in muscle fiber structure. A causal relationship can not be concluded but the acute changes in fiber type distribution and structure suggest that previously reported diaphragm contractile impairment occurs at the level of muscle fibers.

Effects of loaded breathing and hypoxia on diaphragm metabolism as measured by (31)P-NMR spectroscopy.

Diaphragm fatigue may contribute to respiratory failure. (31)P-nuclear magnetic resonance spectroscopy is a useful tool to assess energetic changes within the diaphragm during fatigue, as indicated by P(i) accumulation and phosphocreatine (PCr) depletion. We hypothesized that loaded breathing during hypoxia would lead to diaphragm fatigue and inadequate aerobic metabolism. Seven piglets were anesthetized by using halothane inhalation. Diaphragmatic contractility was assessed by transdiaphragmatic pressure (Pdi) at end expiration with the airway occluded. A nuclear magnetic resonance surface coil placed under the right hemidiaphragm measured P(i) and PCr during four conditions: control, inspiratory resistive breathing (IRB), IRB with hypoxia, and recovery (IRB without hypoxia). IRB alone resulted in hypercarbia (32 +/- 7 to 61 +/- 21 Torr) and respiratory acidosis but no change in diaphragm force output or aerobic metabolism. Combined IRB and hypoxia resulted in decreased force output (Pdi decreased by 40%; from 30 +/- 17 to 19 +/- 11 mmHg) and evidence of metabolic stress (ratio of P(i) to PCr increased by 290%; from 0.19 +/- 0.09 to 0.74 +/- 0.27). We conclude that diaphragm fatigue associated with inadequate aerobic oxidative metabolism occurs in the setting of loaded breathing and hypoxia. Conversely, aerobic metabolism and force output of the diaphragm remain unchanged from control during loaded normoxic or hyperoxic breathing despite the onset of respiratory failure.

In vivo diaphragm metabolism: comparison of paced and inspiratory resistive loaded breathing in piglets.

OBJECTIVE: We hypothesized that spontaneous, loaded diaphragm contractions would lead to diaphragm fatigue, which would correlate with inadequate oxidative metabolism as measured by phosphorus-31 nuclear magnetic resonance spectroscopy. DESIGN: Prospective, randomized, crossover trial. SETTING: University hospital research laboratory. SUBJECTS: Eight piglets, 4 to 6 wks of age. INTERVENTIONS: Each animal underwent, in random order, a 20-min period of diaphragm pacing and a 45-min period of loaded spontaneous breathing, separated by a 20-min recovery period. Mechanical ventilation was used during diaphragm pacing to maintain a PaCO2 of 35 to 45 torr (4.7 to 6.0 kPa) and a PaO2 of > 100 torr (> 13.3 kPa). During spontaneous breathing, inspiratory loading was achieved with a 2.0-mm inner diameter endotracheal tube in the breathing circuit. MEASUREMENTS AND MAIN RESULTS: During pacing, mean transdiaphragmatic pressure decreased by 35%, from 23 +/- 5 (SD) to 15 +/- 3 mm Hg (p < .05), and this decrease correlated with a 335% increase in the ratio of inorganic phosphate to phosphocreatine, from 0.23 +/- 0.1 to 1.0 +/- 0.7 (p < .05). During loaded spontaneous breathing, arterial pH decreased from 7.42 +/- 0.06 to 7.25 +/- 0.05 (p < .05), secondary to an increase in PaCO2 from 41 +/- 4 to 65 +/- 11 torr (5.3 +/- 0.5 to 8.7 +/- 1.5 kPa) (p < .05). Despite respiratory acidosis, there was no decrease in trandiaphragmatic pressure during the period of loaded breathing, nor was any change in the ratio of inorganic phosphate to phosphocreatine seen. CONCLUSIONS: Diaphragm fatigue in a pacing model correlates with inadequate oxidative metabolism. In contrast, severe inspiratory resistive loaded breathing did not result in changes in oxidative metabolism or decreased diaphragm force output, despite hypercapnia and respiratory acidosis.

Ultrasound evaluation of piglet diaphragm function before and after fatigue.

Clinically, a noninvasive measure of diaphragm function is needed. The purpose of this study is to determine whether ultrasonography can be used to 1) quantify diaphragm function and 2) identify fatigue in a piglet model. Five piglets were anesthetized with pentobarbital sodium and halothane and studied during the following conditions: 1) baseline (spontaneous breathing); 2) baseline + CO2 [inhaled CO2 to increase arterial PCO2 to 50-60 Torr (6.6-8 kPa)]; 3) fatigue + CO2 (fatigue induced with 30 min of phrenic nerve pacing); and 4) recovery + CO2 (recovery after 1 h of mechanical ventilation). Ultrasound measurements of the posterior diaphragm were made (inspiratory mean velocity) in the transverse plane. Images were obtained from the midline, just inferior to the xiphoid process, and perpendicular to the abdomen. M-mode measures were made of the right posterior hemidiaphragm in the plane just lateral to the inferior vena cava. Abdominal and esophageal pressures were measured and transdiaphragmatic pressure (Pdi) was calculated during spontaneous (Sp) and paced (Pace) breaths. Arterial blood gases were also measured. Pdi(Sp) and Pdi(Pace) during baseline + CO2 were 8 +/- 0.7 and 49 +/- 11 cmH2O, respectively, and decreased to 6 +/- 1.0 and 27 +/- 7 cmH2O, respectively, during fatigue + CO2. Mean inspiratory velocity also decreased from 13 +/- 2 to 8 +/- 1 cm/s during these conditions. All variables returned to baseline during recovery + CO2. Ultrasonography can be used to quantify diaphragm function and identify piglet diaphragm fatigue.

Afferent activity in pulmonary stretch receptors before and after lung injury.

This study was undertaken to determine the effect of a lung-injury on the activity of slowly adapting pulmonary stretch receptors. Comparisons of receptor activity were made at inhibition of inspiratory (phrenic nerve) activity. The inspiratory activity of these receptors was found to be decreased after lung-injury.