Ralf M. Muellenbach

Prolonged heparin-free extracorporeal membrane oxygenation in multiple injured acute respiratory distress syndrome patients with traumatic brain injury.

BACKGROUND: Extracorporeal membrane oxygenation (ECMO) can be used as an “ultima ratio” strategy in multiple injured patients with severe thoracic trauma. However, systemic anticoagulation during ECMO is recommended and thus traumatic brain injury (TBI) and intracranial bleeding are well-accepted contraindications for ECMO therapy. METHODS: This report describes three cases of prolonged heparin-free venovenous ECMO in multiple injured acute respiratory distress syndrome patients with severe TBI failing conventional mechanical ventilation. RESULTS: Using this strategy, neither ECMO-associated bleeding nor clotting of the extracorporeal circuit occurred. All patients survived. CONCLUSIONS: Based on our experience, we recommend the use of heparin-free ECMO in multiple injured patients with pulmonary failure that is not successfully controlled by lung-protective ventilation even if severe TBI is present. LEVEL OF EVIDENCE: IV, therapeutic study.

Remifentanil for labour analgesia: a meta-analysis of randomised controlled trials

Context Remifentanil is a potent short-acting &mgr;-opioid receptor agonist which is rapidly metabolised in the mother and fetus and may be ideal for labour analgesia. Objectives To assess efficacy and safety of remifentanil compared with other analgesic techniques for labour pain. Data sources We systematically searched the central register of controlled trials of the Cochrane Library (till August 2011) and MEDLINE (till August 2011). Eligibility criteria Randomised controlled trials investigating efficacy and safety of remifentanil administered via a patient-controlled analgesia (PCA) device compared with any other analgesic technique for labour pain were included. Results We finally included 12 randomised controlled trials (published from 2001 to 2011). Women treated with remifentanil had a lower risk of conversion to epidural analgesia (P < 0.001), a lower mean pain score after 1 h (P < 0.001) and had higher satisfaction scores (P < 0.05) in comparison with women receiving pethidine. Epidural analgesia decreased pain scores compared with remifentanil (P = 0.003). There was only a limited amount of data comparing remifentanil with nitrous oxide or fentanyl. Serious maternal or fetal adverse outcomes were not reported in these trials. Conclusion During labour, remifentanil-PCA provided superior analgesia and higher patient satisfaction compared with pethidine with a comparable degree of adverse events. Epidural analgesia provided superior pain relief in comparison with remifentanil. Due to a low number of reported adverse events, the safety issue of remifentanil use in labour remains an open question that needs to be addressed in future trials.

Must we press on until a young mother dies? Remifentanil patient controlled analgesia in labour may not be suited as a "poor man's epidural"

BackgroundThe epidural route is still considered the gold standard for labour analgesia, although it is not without serious consequences when incorrect placement goes unrecognized, e.g. in case of intravascular, intrathecal and subdural placements. Until now there has not been a viable alternative to epidural analgesia especially in view of the neonatal outcome and the need for respiratory support when long-acting opioids are used via the parenteral route. Pethidine and meptazinol are far from ideal having been described as providing rather sedation than analgesia, affecting the cardiotocograph (CTG), causing fetal acidosis and having active metabolites with prolonged half-lives especially in the neonate. Despite these obvious shortcomings, intramuscular and intravenously administered pethidine and comparable substances are still frequently used in delivery units.Since the end of the 90ths remifentanil administered in a patient-controlled mode (PCA) had been reported as a useful alternative for labour analgesia in those women who either don’t want, can’t have or don’t need epidural analgesia.DiscussionIn view of the need for conversion to central neuraxial blocks and the analgesic effect remifentanil has been demonstrated to be superior to pethidine. Despite being less effective in terms of the resulting pain scores, clinical studies suggest that the satisfaction with analgesia may be comparable to that obtained with epidural analgesia. Owing to this fact, remifentanil has gained a place in modern labour analgesia in many institutions.However, the fact that remifentanil may cause harm should not be forgotten when the use of this potent mu-agonist is considered for the use in labouring women. In the setting of one-to-one midwifery care, appropriate monitoring and providing that enough experience exists with this potent opioid and the treatment of potential complications, remifentanil PCA is a useful option in addition to epidural analgesia and other central neuraxial blocks. Already described serious consequences should remind us not refer to remifentanil PCA as a “poor man’s epidural” and to safely administer remifentanil with an appropriate indication.SummaryTherefore, the authors conclude that economic considerations and potential cost-savings in conjunction with remifentanil PCA may not be appropriate main endpoints when studying this valuable method for labour analgesia.

Controlled transient hypercapnia: a novel approach for the treatment of delayed cerebral ischemia after subarachnoid hemorrhage?

OBJECT The authors undertook this study to investigate whether the physiological mechanism of cerebral blood flow (CBF) regulation by alteration of the arterial partial pressure of carbon dioxide (PaCO₂) can be used to increase CBF after aneurysmal subarachnoid hemorrhage (aSAH). METHODS In 6 mechanically ventilated patients with poor-grade aSAH, the PaCO₂ was first decreased to 30 mm Hg by modification of the respiratory rate, then gradually increased to 40, 50 and 60 mm Hg for 15 minutes each setting. Thereafter, the respirator settings were returned to baseline parameters. Intracerebral CBF measurement and brain tissue oxygen saturation (StiO₂), measured by near-infrared spectroscopy (NIRS), were the primary and secondary end points. Intracranial pressure (ICP) was controlled by external ventricular drainage. RESULTS A total of 60 interventions were performed in 6 patients. CBF decreased to 77% of baseline at a PaCO₂ of 30 mm Hg and increased to 98%, 124%, and 143% at PaCO₂ values of 40, 50, and 60 mm Hg, respectively. Simultaneously, StiO₂ decreased to 94%, then increased to 99%, 105%, and 111% of baseline. A slightly elevated delivery rate of cerebrospinal fluid was noticed under continuous drainage. ICP remained constant. After returning to baseline respirator settings, both CBF and StiO₂ remained elevated and only gradually returned to pre-hypercapnia values without a rebound effect. None of the patients developed secondary cerebral infarction. CONCLUSIONS Gradual hypercapnia was well tolerated by poor-grade SAH patients. Both CBF and StiO₂ reacted with a sustained elevation upon hypercapnia; this elevation outlasted the period of hypercapnia and only slowly returned to normal without a rebound effect. Elevations of ICP were well compensated by continuous CSF drainage. Hypercapnia may yield a therapeutic potential in this state of critical brain perfusion. Clinical trial registration no.: NCT01799525 ( ClinicalTrials.gov ).

An in-vivo Metabolic Test for Detecting Malignant Hyperthermia Susceptibility in Humans: A Pilot Study

INTRODUCTION:In vitro contracture testing to diagnose malignant hyperthermia (MH) susceptibility requires a muscle biopsy, which may be associated with severe side effects for the patient. After investigation of several different protocols, we present a less invasive metabolic test that involves IM injection of caffeine and halothane, and subsequent measurement of interstitial lactate to differentiate between MH susceptible (MHS) and MH non-susceptible (MHN) individuals. METHODS:Two microdialysis probes with attached microtubing for trigger injection were inserted into the lateral vastus muscle of eight previously diagnosed MHS patients (representing three genetic variants Gly2434Arg, Thr2206Met, and Arg614Cys), seven MHN patients, and seven control individuals. After equilibration and lactate baseline recording, a single bolus of 200 μL caffeine 80 mM and a suspension of 200 μL halothane 4%V/V in soy bean oil (triggers) were injected locally. Lactate was measured spectrophotometrically. Data are presented as medians and interquartile ranges. RESULTS:Although baseline lactate values were similar in the investigated groups before trigger injection, caffeine increased local lactate in MHS patients significantly more (2.0 [1.8–2.6] mM) than in MHN (0.8 [0.6–1.1] mM) or in control individuals (0.8 [0.6–0.8 mM]). Similarly, halothane lead to a significant lactate increase in MHS compared to MHN and control individuals (8.6 [3.7–8.9] mM vs 0.9 [0.5–1.1] mM and 1.7 [0.9–2.3] mM, respectively). However, a relevant increase of lactate was observed in one MHN and in two control individuals. Systemic hemodynamic and metabolic variables did not differ between the investigated groups. DISCUSSION:Metabolic monitoring of IM lactate after local caffeine and halothane injection may allow less invasive testing to detect MH susceptibility, without systemic side effects.

Clinical implications of Mycobacterium chimaera detection in thermoregulatory devices used for extracorporeal membrane oxygenation (ECMO), Germany, 2015 to 2016

Mycobacterium chimaera, a non-tuberculous mycobacterium, was recently identified as causative agent of deep-seated infections in patients who had previously undergone open-chest cardiac surgery. Outbreak investigations suggested an aerosol-borne pathogen transmission originating from water contained in heater-cooler units (HCUs) used during cardiac surgery. Similar thermoregulatory devices are used for extracorporeal membrane oxygenation (ECMO) and M. chimaera might also be detectable in ECMO treatment settings. We performed a prospective microbiological study investigating the occurrence of M. chimaera in water from ECMO systems and in environmental samples, and a retrospective clinical review of possible ECMO-related mycobacterial infections among patients in a pneumological intensive care unit. We detected M. chimaera in 9 of 18 water samples from 10 different thermoregulatory ECMO devices; no mycobacteria were found in the nine room air samples and other environmental samples. Among 118 ECMO patients, 76 had bronchial specimens analysed for mycobacteria and M. chimaera was found in three individuals without signs of mycobacterial infection at the time of sampling. We conclude that M. chimaera can be detected in water samples from ECMO-associated thermoregulatory devices and might potentially pose patients at risk of infection. Further research is warranted to elucidate the clinical significance of M. chimaera in ECMO treatment settings.

The contribution of arterio-venous extracorporeal lung assist to gas exchange in a porcine model of lavage-induced acute lung injury

This prospective large-animal study was performed to evaluate the contribution of arterio-venous extracorporeal lung assist (AV-ECLA) to pulmonary gas exchange in a porcine lavage-induced acute lung injury model. Fifteen healthy female pigs, weighing 50.39±3.8 kg (mean±SD), were included. After induction of general anaesthesia and controlled ventilation, an arterial line and a pulmonary artery catheter were inserted. Saline lung lavage was performed until the PaO2 decreased to 51±16 mmHg. After a stabilization period of 60 min, the femoral artery and vein were cannulated and a low-resistance membrane lung was interposed. Under apnoeic oxygenation, variations of sweep-gas flow were performed every 20 min in order to evaluate the membrane lungs efficacy, in terms of carbon dioxide (CO2) removal and oxygen (O2) uptake. Although AV-ECLA is highly effective in eliminating CO2, if combined with apnoeic oxygenation, normocapnia was not achievable. AV-ECLAs contribution to oxygenation during severe hypoxemia was antagonized by a significant increase in the pulmonary shunt fraction.

Cerebral tissue oxygenation during the initiation of venovenous ECMO.

In an acute respiratory distress syndrome, venovenous extracorporeal membrane oxygenation (vvECMO) can rapidly normalize arterial hypoxemia and carbon dioxide tension (PaCO2). Considering the positive relationship between PaCO2 and cerebral blood flow, the aim of the current study was to evaluate cerebral regional tissue oxygen saturation (rSO2) during the implementation of vvECMO. Fifteen acute respiratory distress syndrome patients with recordings of cerebral rSO2 by near-infrared spectroscopy before vvECMO implementation until the optimization of the ECMO/ventilator settings were retrospectively studied. Results: median (interquartile range). The cerebral rSO2 increased significantly (p < 0.05) from 69(61–74) to 75(60–80)% after ECMO was started, concomitant to the arterial oxygenation. Until the end of the observation period after 83(44–132) minutes, cerebral rSO2 decreased significantly to 61(52–71)%. PaCO2 decreased from 70(61–87) to 43(38–54) mm Hg and the pH increased from 7.23(7.14–7.29) to 7.39(7.34–7.43). The baseline arterial oxygen saturation and tension as well as the actual bicarbonate concentration were negatively correlated with the absolute change in cerebral rSO2 (&Dgr;rSO2). In the 11 nonhypoxemic patients (arterial oxygen saturation ≥90%) &Dgr;PaCO2 was significantly correlated with &Dgr;rSO2. Patients receiving vvECMO treatment are at risk for a decrease in cerebral rSO2. This decrease is more distinct in patients with normal baseline arterial oxygenation and high actual bicarbonate.

High frequency oscillatory ventilation and prone positioning in a porcine model of lavage-induced acute lung injury

BackgroundThis animal study was conducted to assess the combined effects of high frequency oscillatory ventilation (HFOV) and prone positioning on pulmonary gas exchange and hemodynamics.MethodsSaline lung lavage was performed in 14 healthy pigs (54 ± 3.1 kg, mean ± SD) until the arterial oxygen partial pressure (PaO2) decreased to 55 ± 7 mmHg. The animals were ventilated in the pressure controlled mode (PCV) with a positive endexpiratory pressure (PEEP) of 5 cmH2O and a tidal volume (VT) of 6 ml/kg body weight. After a stabilisation period of 60 minutes, the animals were randomly assigned to 2 groups. Group 1: HFOV in supine position; group 2: HFOV in prone position. After evaluation of prone positioning in group 2, the mean airway pressure (Pmean) was increased by 3 cmH2O from 16 to 34 cmH2O every 20 minutes in both groups accompanied by measurements of respiratory and hemodynamic variables. Finally all animals were ventilated supine with PCV, PEEP = 5 cm H2O, VT = 6 ml/kg.ResultsCombination of HFOV with prone positioning improves oxygenation and results in normalisation of cardiac output and considerable reduction of pulmonary shunt fraction at a significant (p < 0.05) lower Pmean than HFOV and supine positioning.ConclusionIf ventilator induced lung injury is ameliorated by a lower Pmean, a combined treatment approach using HFOV and prone positioning might result in further lung protection.

Effects of Fluid Treatment With Hydroxyethyl Starch on Renal Function in Patients With Aneurysmal Subarachnoid Hemorrhage.

Background: Recent reports have doubted the efficacy and safety of hydroxyethyl starch (HES) for volume resuscitation. HES has been reported to promote renal insufficiency particularly in sepsis and trauma patients. This analysis investigated the effects of HES 6% 130/0.4 for fluid therapy in patients with intact renal function who suffered aneurysmal subarachnoid hemorrhage (SAH). Methods: This retrospective analysis included 107 patients and was conducted in the framework of a clinical trial assessing the efficacy of magnesium sulfate in SAH. Because magnesium is renally eliminated, patients with renal insufficiency had been excluded. Standard therapy after aneurysm occlusion included the daily administration of HES 6% 130/0.4. Serum and urine creatinine and fluid balance were measured daily. Results: Patients received a daily mean of 1101±524 mL HES and 3353±1396 mL Ringer’s solution. The highest creatinine values were recorded on day 3 after admission (0.88±0.25 mg/100 mL) and continuously decreased thereafter. In 6 patients, creatinine values temporarily increased by >0.3 mg/100 mL but recovered to admission values at the end of the observation period. Conclusions: Concerning renal function, the first days after SAH seem to be a vulnerable phase in which a variety of interventions are performed, including contrast-enhanced neuroradiologic procedures. In this period, HES 6% 130/0.4 should be administered with caution. However, no patient suffered from renal failure and required temporary or permanent renal replacement therapy. These results suggest that the administration of HES 6% 130/0.4 is safe in SAH patients without preexisting renal insufficiency.