Effect of induced hypothermia on respiratory parameters in mechanically ventilated patients

Aim: Mild hypothermia is increasingly applied in the intensive care unit. Knowledge on the effects of hypothermia on respiratory parameters during mechanical ventilation is limited. In this retrospective study, we describe the effect of hypothermia on gas exchange in patients cooled for 24 h after a cardiac arrest. Methods: Respiratory parameters were derived from electronic patient files from 65 patients at the start and end of the hypothermic phase and at every centigrade increase in body temperature until normo-temperature, including tidal volume, positive end expiratory pressure (PEEP), plateau pressure, respiratory rate, exhaled CO2 concentrations (etCO(2)) and FIO2. Static compliance was calculated as V-T/P-plateau - PEEP. Dead space ventilation was calculated as (PaCO2-etCO(2))/PaCO2. Results: During hypothermia, PaCO2 decreased, at unchanged PaCO2-etCO(2) gap and minute ventilation. During rewarming, PaCO2 did not change, while etCO(2) increased at unchanged minute ventilation. Dead space ventilation did not change during hypothermia, but lowered during rewarming. During hypothermia, PaO2/FIO2 ratio increased at unchanged PEEP levels. Respiratory static compliance did not change during hypothermia, nor during rewarming. Conclusion: Hypothermia possibly improves oxygenation and ventilation in mechanically ventilated patients. Results may accord with the hypothesis that reducing metabolism with applied hypothermia may be beneficial in patients with acute lung injury, in whom low minute ventilation results in severe hypercapnia. (C) 2010 Elsevier Ireland Ltd. All rights reserve

Suspended animation inducer hydrogen sulfide is protective in an in vivo model of ventilator-induced lung injury

Acute lung injury is characterized by an exaggerated inflammatory response and a high metabolic demand. Mechanical ventilation can contribute to lung injury, resulting in ventilator-induced lung injury (VILI). A suspended-animation-like state induced by hydrogen sulfide (H2S) protects against hypoxia-induced organ injury. We hypothesized that suspended animation is protective in VILI by reducing metabolism and thereby CO2 production, allowing for a lower respiratory rate while maintaining adequate gas exchange. Alternatively, H2S may reduce inflammation in VILI. In mechanically ventilated rats, VILI was created by application of 25 cmH(2)O positive inspiratory pressure (PIP) and zero positive end-expiratory pressure (PEEP). Controls were lung-protective mechanically ventilated (13 cmH(2)O PIP, 5 cmH(2)O PEEP). H2S donor NaHS was infused continuously; controls received saline. In separate control groups, hypothermia was induced to reproduce the H2S-induced fall in temperature. In VILI groups, respiratory rate was adjusted to maintain normo-pH. NaHS dose-dependently and reversibly reduced body temperature, heart rate, and exhaled amount of CO2. In VILI, NaHS reduced markers of pulmonary inflammation and improved oxygenation, an effect which was not observed after induction of deep hypothermia that paralleled the NaHS-induced fall in temperature. Both NaHS and hypothermia allowed for lower respiratory rates while maintaining gas exchange. NaHS reversibly induced a hypometabolic state in anesthetized rats and protected from VILI by reducing pulmonary inflammation, an effect that was in part independent of body temperatur

Induced hypothermia is associated with reduced circulating subunits of mitochondrial DNA in cardiac arrest patients

Induced hypothermia may protect from ischemia reperfusion injury. The mechanism of protection is not fully understood and may include an effect on mitochondria. Here we describe the effect of hypothermia on circulating mitochondrial (mt) DNA in a substudy of a multicenter randomized trial (the Target Temperature Management trial). Circulating levels of mtDNA were elevated in patients with cardiac arrest at all-time points compared to healthy controls. After 24 h of temperature management, patients kept at 33 °C had significantly lower levels of COX3, NADH1 and NADH2 compared to baseline, in contrast to those kept at 36 °C. After regain of temperature, cytochrome - B was significantly reduced in patients kept at 33 °C with cardiac arrest. Cardiac arrest results in circulating mtDNA levels, which reduced during a temperature management protocol in patients with a target temperature of 33 °

Heliox allows for lower minute volume ventilation in an animal model of ventilator-induced lung injury

Helium is a noble gas with a low density, allowing for lower driving pressures and increased carbon dioxide (CO2) diffusion. Since application of protective ventilation can be limited by the development of hypoxemia or acidosis, we hypothesized that therefore heliox facilitates ventilation in an animal model of ventilator-induced lung injury. Sprague-Dawley rats (N=8 per group) were mechanically ventilated with heliox (50% oxygen; 50% helium). Controls received a standard gas mixture (50% oxygen; 50% air). VILI was induced by application of tidal volumes of 15 mL kg(-1); lung protective ventilated animals were ventilated with 6 mL kg(-1). Respiratory parameters were monitored with a pneumotach system. Respiratory rate was adjusted to maintain arterial pCO2 within 4.5-5.5 kPa, according to hourly drawn arterial blood gases. After 4 hours, bronchoalveolar lavage fluid (BALF) was obtained. Data are mean (SD). VILI resulted in an increase in BALF protein compared to low tidal ventilation (629 (324) vs. 290 (181) μg mL(-1); p <0.05) and IL-6 levels (640 (8.7) vs. 206 (8.7) pg mL(-1); p <0.05), whereas cell counts did not differ between groups after this short course of mechanical ventilation. Ventilation with heliox resulted in a decrease in mean respiratory minute volume ventilation compared to control (123 ± 0.6 vs. 146 ± 8.9 mL min(-1), P <0.001), due to a decrease in respiratory rate (22 (0.4) vs. 25 (2.1) breaths per minute; p <0.05), while pCO2 levels and tidal volumes remained unchanged, according to protocol. There was no effect of heliox on inspiratory pressure, while compliance was reduced. In this mild lung injury model, heliox did not exert anti-inflammatory effects. Heliox allowed for a reduction in respiratory rate and respiratory minute volume during VILI, while maintaining normal acid-base balance. Use of heliox may be a useful approach when protective tidal volume ventilation is limited by the development of severe acidosi

Inflammatory parameters in an animal model of ventilator–induced lung injury (N=8 per group), treated with heliox ventilation.

<div><p>Heliox is marked by white bars and oxygen/air by grey bars. Data are MEAN ± SEM. *: P < 0.05; **: P < 0.01. </p> <p>(A) Protein levels; (B) IL- 6 levels; (C) CINC–3 levels and (D) cell count in bronchoalveolar lavage fluid. </p></div

Induced hypothermia is protective in a rat model of pneumococcal pneumonia associated with increased adenosine triphosphate availability and turnover

Objective: To determine the effect of induced hypothermia on bacterial growth, lung injury, and mitochondrial function in a rat model of pneumococcal pneumosepsis. Design: Animal study. Setting: University research laboratory. Subjects: Male Sprague-Dawley rats. Interventions: Subjects were inoculated intratracheally with Streptococcus pneumoniae and controls received saline. After the development of pneumonia, mechanical ventilation was started with or without induced mild hypothermia (32 degrees C). Bacterial growth and inflammatory markers were determined in bronchoalveolar lavage fluid, blood, and organs. Oxidative phosphorylation and adenosine triphosphate contents were measured in mitochondria isolated from the liver and soleus muscle. Measurements and Main Results: Inoculation with S. pneumoniae resulted in severe pneumonia with bacterial dissemination, distal organ injury, and blunted peripheral oxygen consumption on mechanical ventilation. Hypothermia did not affect bacterial growth in bronchoalveolar lavage fluid and in homogenized lungs compared with normothermic controls but was associated with reduced bacterial dissemination to the spleen with a trend toward reduced bacterial load in blood and liver. Hypothermia reduced lung injury, exemplified by reductions in pulmonary cell influx and bronchoalveolar lavage fluid protein levels compared with controls. Hypothermia reduced bronchoalveolar lavage fluid levels of interleukin-1 beta, tended to reduce bronchoalveolar lavage fluid CINC-3 levels, but no effect was observed on bronchoalveolar lavage fluid tumor necrosis factor-a and interleukin-6 levels. Induced hypothermia restored the fall in oxygen consumption and adenosine triphosphate levels in the liver, whereas adenosine triphosphate/adenosine diphosphate ratios remained low. In muscle, induced hypothermia also reversed low oxygen consumption as a result of pneumonia, but with an increase in adenosine triphosphate levels, whereas adenosine triphosphate/adenosine diphosphate ratios were low. Conclusion: Hypothermia did not adversely affect bacterial growth, but rather reduced bacterial dissemination in a rat model of pneumococcal pneumosepsis. Furthermore, hypothermia reduced lung injury associated with restored adenosine triphosphate availability and turnover. These findings suggest that hypothermia may reduce organ injury by preventing sepsis-related mitochondria! dysfunction. (Crit Care Med 2012; 40:919-926

Respiratory parameters in an animal model of lung injury during treatment with heliox ventilation (N=8 per group).

<div><p>Data are MEAN ± SEM. VILI is marked by open triangles; LP ventilation is marked by filled circles. Heliox ventilation is marked by a disconnected line and oxygen/air by a continuous line. Comparisons are between heliox and oxygen within the VILI or the LP group. *: P < 0.05; **: P < 0.01; ***: P < 0.001.</p> <p>(A) Minute volume ventilation (mL min^-1); (B) respiratory rate (breaths per min); (C) inspiratory pressure (cm H₂O); (D ) mean airway pressure (cm H₂O); (E ) tidal volume (mL kg^-1); (F) A-a gradient; (G) dead space (mmHg) and (H) compliance (mL cm H₂O ^-1). </p></div

Prolonged Helium Postconditioning Protocols during Early Reperfusion Do Not Induce Cardioprotection in the Rat Heart In Vivo: Role of Inflammatory Cytokines

Postconditioning of myocardial tissue employs short cycles of ischemia or pharmacologic agents during early reperfusion. Effects of helium postconditioning protocols on infarct size and the ischemia/reperfusion-induced immune response were investigated by measurement of protein and mRNA levels of proinflammatory cytokines. Rats were anesthetized with S-ketamine (150 mg/kg) and diazepam (1.5 mg/kg). Regional myocardial ischemia/reperfusion was induced; additional groups inhaled 15, 30, or 60 min of 70% helium during reperfusion. Fifteen minutes of helium reduced infarct size from 43% in control to 21%, whereas 30 and 60 minutes of helium inhalation led to an infarct size of 47% and 39%, respectively. Increased protein levels of cytokine-induced neutrophil chemoattractant (CINC-3) and interleukin-1 beta (IL-1 ) were found after 30 or 60 min of helium inhalation, in comparison to control. 30 min of helium increased mRNA levels of CINC-3, IL-1 , interleukin 6 (IL-6), and tumor necrosis factor alpha (TNF-) in myocardial tissue not directly subjected to ischemia/reperfusion. These results suggest that the effectiveness of the helium postconditioning protocol is very sensitive to duration of noble gas application. Additionally, helium was associated with higher levels of inflammatory cytokines; however, it is not clear whether this is causative of nature or part of an epiphenomenon