Ulf Guenther

Tidal recruitment assessed by electrical impedance tomography and computed tomography in a porcine model of lung injury

Objectives:To determine the validity of electrical impedance tomography to detect and quantify the amount of tidal recruitment caused by different positive end-expiratory pressure levels in a porcine acute lung injury model. Design:Randomized, controlled, prospective experimental study. Setting:Academic research laboratory. Subjects:Twelve anesthetized and mechanically ventilated pigs. Interventions:Acute lung injury was induced by central venous oleic acid injection and abdominal hypertension in seven animals. Five healthy pigs served as control group. Animals were ventilated with positive end-expiratory pressure of 0, 5, 10, 15, 20, and 25 cm H2O, respectively, in a randomized order. Measurements and Main Results:At any positive end-expiratory pressure level, electrical impedance tomography was obtained during a slow inflation of 12 mL/kg of body weight. Regional-ventilation-delay indices quantifying the time until a lung region reaches a certain amount of impedance change were calculated for lung quadrants and for every single electrical impedance tomography pixel, respectively. Pixel-wise calculated regional-ventilation-delay indices were plotted in a color-coded regional-ventilation-delay map. Regional-ventilation-delay inhomogeneity that quantifies heterogeneity of ventilation time courses was evaluated by calculating the scatter of all pixel-wise calculated regional-ventilation-delay indices. End-expiratory and end-inspiratory computed tomography scans were performed at each positive end-expiratory pressure level to quantify tidal recruitment of the lung. Tidal recruitment showed a moderate inter-individual (r = .54; p < .05) and intra-individual linear correlation (r = .46 up to r = .73 and p < .05, respectively) with regional-ventilation-delay obtained from lung quadrants. Regional-ventilation-delay inhomogeneity was excellently correlated with tidal recruitment intra- (r = .90 up to r = .99 and p < .05, respectively) and inter-individually (r = .90; p < .001). Conclusions:Regional-ventilation-delay can be noninvasively measured by electrical impedance tomography during a slow inflation of 12 mL/kg of body weight and visualized using ventilation delay maps. Our experimental data suggest that the impedance tomography-based analysis of regional-ventilation-delay inhomogeneity provides a good estimate of the amount of tidal recruitment and may be useful to individualize ventilatory settings.

Delirium in the postanaesthesia period

Purpose of review Delirium is an acute, potentially life-threatening organ dysfunction with an incidence reported to range from 10–70% after surgery. Postoperative delirium was found to be associated with persisting cognitive deficits, increased physical dependence and institutionalization, and increased mortality. It is a condition particularly relevant to patients with increasing age. Recent findings This study summarizes recent works of the past 2 years, giving a brief overview as well as background information with regard to risk factors, impact on outcome parameters, mechanisms of pathophysiology, current use of hospital medication, and prevention and treatment strategies of postoperative delirium. Summary Delirium may have an impact on patients’ outcomes beyond their stay in hospital, depending on preoperative comorbidities. Delirium can be devastating for activity of daily living, cognitive performance and survival. Predisposing factors should be recognized preoperatively; precipitating factors such as preoperative fasting, deep sedation and choice of psychotropic drugs, including sedatives, should be reconsidered. Regular structured delirium screening is the precondition for early detection and treatment. Treatment options include cognitive training programmes, anti-inflammatory measures and antipsychotic drugs.

Extended therapeutic hypothermia for several days during extracorporeal membrane-oxygenation after drowning and cardiac arrest Two cases of survival with no neurological sequelae.

Drowning associated with hypothermia and cardiopulmonary resuscitation has a very poor prognosis. We report two such cases, where impossible oxygenation due to severe pulmonary oedema was treated with extracorporeal membrane-oxygenation (ECMO). Following cardiac arrest, mild therapeutic hypothermia for 24h was maintained as recommended, but subsequent rewarming precipitated additional pulmonary oedema. Little is currently known about how long to maintain therapeutic hypothermia to optimize neurological outcome and suppress reperfusion injury. In our patients, therapeutic hypothermia during veno-venous ECMO-treatment was extended for up to 6 days. Both patients survived with no neurological sequelae. We speculate that prolonged hypothermia was not only neuroprotective, but also minimized reperfusion injury including pulmonary oedema. Extension of hypothermia for several days seems safe and feasible in selected cases.

The Counteraction of Opioid-induced Ventilatory Depression by the Serotonin 1a-agonist 8-oh-dpat Does Not Antagonize Antinociception in Rats in Situ and in Vivo

BACKGROUND: Spontaneous breathing during mechanical ventilation is gaining increasing importance during intensive care but is depressed by narcotics, such as opioids. Serotonin 1A-receptor (5-HT1A-R) agonists have been shown to antagonize opioid-induced ventilatory depression, but both enhancement and attenuation of nociceptive reflexes have been found with different experimental models. To clarify contradictory findings, we simultaneously determined dose-response functions of the standard 5-HT1A-R-agonist 8-OH-DPAT and two different opioids for spontaneous ventilation and nociception. Two hypotheses were tested: 1) 8-OH-DPAT at a dose to stimulate spontaneous breathing does not activate nociceptive reflexes. 2) 8-OH-DPAT does not diminish opioid-induced antinociception. METHODS: (A) A dose-response relationship of 8-OH-DPAT, spontaneous phrenic nerve activity and a nociceptive C-fiber reflex (CFR) were established simultaneously in an in situ perfused, nonanesthetized, rat brainstem-spinal cord preparation. (B) Fentanyl was administered in situ to investigate the interaction with 8-OH-DPAT on phrenic nerve activity and nociceptive CFR. Additional experiments involved the selective 5-HT1A-R-antagonist WAY 100 635 to exclude effects of receptors other than 5-HT1A-R

Cardiorespiratory effects of spontaneous breathing in two different models of experimental lung injury : a randomized controlled trial

IntroductionAcute lung injury (ALI) can result from various insults to the pulmonary tissue. Experimental and clinical data suggest that spontaneous breathing (SB) during pressure-controlled ventilation (PCV) in ALI results in better lung aeration and improved oxygenation. Our objective was to evaluate whether the addition of SB has different effects in two different models of ALI.MethodsForty-four pigs were randomly assigned to ALI resulting either from hydrochloric acid aspiration (HCl-ALI) or from increased intra-abdominal pressure plus intravenous oleic acid injections (OA-ALI) and were ventilated in PCV mode either with SB (PCV + SB) or without SB (PCV – SB). Cardiorespiratory variables were measured at baseline after induction of ALI and after 4 hours of treatment (PCV + SB or PCV – SB). Finally, density distributions and end-expiratory lung volume (EELV) were assessed by thoracic spiral computed tomography.ResultsPCV + SB improved arterial partial pressure of oxygen/inspiratory fraction of oxygen (PaO2/FiO2) by a reduction in intrapulmonary shunt fraction in HCl-ALI from 27% ± 6% to 23% ± 13% and in OA-ALI from 33% ± 19% to 26% ± 18%, whereas during PCV – SB PaO2/FiO2 deteriorated and shunt fraction increased in the HCl group from 28% ± 8% to 37% ± 17% and in the OA group from 32% ± 12% to 47% ± 17% (P < 0.05 for interaction time and treatment, but not ALI type). PCV + SB also resulted in higher EELV (HCl-ALI: 606 ± 171 mL, OA-ALI: 439 ± 90 mL) as compared with PCV – SB (HCl-ALI: 372 ± 130 mL, OA-ALI: 192 ± 51 mL, with P < 0.05 for interaction of time, treatment, and ALI type).ConclusionsSB improves oxygenation, reduces shunt fraction, and increases EELV in both models of ALI.

Patients prone for postoperative delirium: preoperative assessment, perioperative prophylaxis, postoperative treatment.

Purpose of review The aim of this study was to review current literature on identification of patients at risk for postoperative delirium (POD) and to summarize recent findings on prophylaxis and treatment. Recent findings Age and preoperative cognitive impairment are among the most important risk factors of POD. POD is the result of a complex interplay of predisposing and precipitating factors. Thus, both prophylaxis and treatment require multicomponent intervention programs. No single medication to prevent or treat POD is available. Avoiding too deep anesthesia, avoiding additional psychoactive substances including benzodiazepines and intravenous opioids, and effective pain management as well as early mobilization are essential. Summary An increase of the proportion of elderly patients undergoing surgery will lead to a higher incidence of POD. Preoperative assessment should facilitate identification of patients at high risk. Perioperative management should include monitoring depth of anesthesia, preference for nonopioid pain therapy, early regular delirium monitoring starting in the recovery room, avoiding ICU-sedation, early mobilization and exercise, and cognitive training.

Repinotan, a selective 5-HT1A-R-agonist, antagonizes morphine-induced ventilatory depression in anesthetized rats.

BACKGROUND:Spontaneous breathing during mechanical ventilation improves arterial oxygenation and cardiovascular function, but is depressed by opioids during critical care. Opioid-induced ventilatory depression was shown to be counteracted in anesthetized rats by serotonin(1A)-receptor (5-HT1A-R)-agonist 8-OH-DPAT, which cannot be applied to humans. Repinotan hydrochloride is a selective 5-HT1A-R-agonist already investigated in humans, but the effects on ventilation and nociception are unknown. In this study, we sought to establish (a) the effects of repinotan on spontaneous breathing and nociception, and (b) the interaction with the standard opiate morphine. METHODS:The dose-dependent effects of repinotan, given alone or in combination with morphine, on spontaneous minute ventilation (MV) and nociceptive tail-flick reflex latencies (TFLs) were measured simultaneously in spontaneously breathing anesthetized rats. An additional series with NaCl 0.9% and the 5-HT1A-R-antagonist WAY 100 135 served as controls. RESULTS:(a) Repinotan dose-dependently activated spontaneous breathing (MV, mean [95% confidence interval]; 53% [29%–77%]) of pretreatment level) and suppressed nociception (TLF, 91% maximum possible effect [68%–114%]) with higher doses of repinotan (2–200 &mgr;g/kg). On the contrary, nociception was enhanced with a small dose of repinotan (0.2 &mgr;g/kg; TFL, −47% maximum possible effect [−95% to 2%]). Effects were prevented by 5-HT1A-antagonist WAY 100 135. (B) Morphine-induced depression of ventilation (MV, −72% [−100% to −44%]) was reversed by repinotan (20 &mgr;g/kg), which returned spontaneous ventilation to pretreatment levels (MV, 18% [−40% to 77%]). The morphine-induced complete depression of nociception was sustained throughout repinotan and NaCl 0.9% administration. Despite a mild decrease in mean arterial blood pressure, there were no serious cardiovascular side effects from repinotan. CONCLUSIONS:The 5-HT1A-R-agonist repinotan activates spontaneous breathing in anesthetized rats even in morphine-induced ventilatory depression. The potency of 5-HT1A-R-agonists to stimulate spontaneous breathing and their antinociceptive effects should be researched further.

Selective 5-HT1A-R-agonist Repinotan Prevents Remifentanil-induced Ventilatory Depression and Prolongs Antinociception

Background: 5-HT1A-R-agonist repinotan was shown to counteract a morphine-induced ventilatory depression but had pronociceptive effects at small doses (0.2 &mgr;g/kg). It remained to be clarified (1) whether a moderate dose of repinotan, sufficient to stimulate spontaneous breathing, impairs antinociception if plasma concentration decreases over time, and if (2) moderate doses prevent ventilatory depression if given before the opioid. Methods: A dose–response curve of the repinotan effects on spontaneous minute ventilation during continuous remifentanil infusion in anesthetized rats was established to identify moderate doses: (1) tail-flick reflex latencies to assess nociception were recorded until 60 min after cessation of a continuous remifentanil infusion with or without a concomitant moderate repinotan dose (10 &mgr;g/kg), and (2) remifentanil boluses (2.5 &mgr;g/kg) were given after repinotan (10 and 20 &mgr;g/kg). Results: (1) Remifentanil-induced antinociception lasted only 5 min after infusion was stopped (tail-flick reflex latencies; median [interquartile range], 97 [54–100]% of maximum possible effect; P = 0.034), but was extended by repinotan (10 &mgr;g/kg) to 30 min (tail-flick reflex latencies, 100 [75–100]% of maximum possible effect; P = 0.031). Repinotan (10 &mgr;g/kg) alone did not have any significant antinociceptive effect. (2) The ventilatory depression by remifentanil boluses (2.5 &mgr;g/kg; minute ventilation, −65 [−81to −56]%; P = 0.031, n = 5) was blunted by repinotan (20 &mgr;g/kg; minute ventilation, −24 [−53 to 13]%; P = 0.313, compared with the pretreatment level). Conclusions: Repinotan prevented remifentanil-induced ventilatory depression in spontaneously breathing, anesthetized rats. Although repinotan did not depress nociception itself, it prolonged the profound antinociception after discontinuation of remifentanil infusion.

Hemorrhage under veno-venous extracorporeal membrane oxygenation in acute respiratory distress syndrome patients: a retrospective data analysis

Background Despite being still invasive and challenging, technical improvement has resulted in broader and more frequent application of extracorporeal membrane oxygenation (ECMO), to prevent hypoxemia and to reduce invasiveness of mechanical ventilation (MV). Heparin-coated ECMO-circuits are currently standard of care, in addition to heparin based anticoagulation (AC) regimen guided by activated clotting time (ACT) or activated partial thromboplastin time (aPTT). Despite these advances, a reliable prediction of hemorrhage is difficult and the risk of hemorrhagic complication remains unfortunately high. We hypothesized, that there are coagulation parameters that are indices for a higher risk of hemorrhage under veno-venous (VV)-ECMO therapy. Methods Data from 36 patients with severe respiratory failure treated with VV-ECMO at a University Hospital intensive care unit (ICU) were analyzed retrospectively. Patients were separated into two groups based on severity of hemorrhagic complications and transfusion requirements. The following data were collected: demographics, hemodynamic data, coagulation samples, transfusion requirements, change of ECMO-circuit during treatment and adverse effects, including hemorrhage and thrombosis. Results In this study 74 hemorrhagic events were observed, one third of which were severe. Patients suffering from severe hemorrhage had a lower survival rate on VV-ECMO (43% vs. 91%; P=0.002) and in ICU (36% vs. 86%; P=0.002). SAPS II, factor VII and X were different between mild and severe hemorrhage group. Conclusions Severe hemorrhage under VV-ECMO is associated with higher mortality. Only factor VII and X differed between groups. Further clinical studies are required to determine the timing of initiation and targets for AC therapies during VV-ECMO.

Malignant hyperthermia as a rare cause of SIRS after cardiac surgery

Background Use of extracorporal circulation (cardiopulmonary bypass) during cardiac surgery can cause a systemic inflammatory response. This so called “post-perfusionsyndrome” (PPS) occurs in about a quarter of patients and results in clinical signs and symptoms of “systemic inflammatory response syndrome” (SIRS) in 2-10% of patients. This condition is clinically associated with mild hyperthermia, acidosis, tachycardia and vasoplegia. It is generally treated with cristalloid infusions and vasopressors, and is mostly subsided by the next morning, at the latest after 48h. Malignant hyperthermia is associated with a severe combined (respiratory and metabolic) acidosis, hyperlactatemia, hypercapnia, hyperthermia, grossly elevated serum levels of creatine kinase (CK) and acute renal failure.