[Show abstract][Hide abstract] ABSTRACT: Remote ischemic preconditioning (RIPC) is reported to reduce biomarkers of ischemic and reperfusion injury in patients undergoing cardiac surgery, but uncertainty about clinical outcomes remains. METHODS We conducted a prospective, double-blind, multicenter, randomized, controlled trial involving adults who were scheduled for elective cardiac surgery requiring cardiopulmonary bypass under total anesthesia with intravenous propofol. The trial compared upper-limb RIPC with a sham intervention. The primary end point was a composite of death, myocardial infarction, stroke, or acute renal failure up to the time of hospital discharge. Secondary end points included the occurrence of any individual component of the primary end point by day 90. RESULTS A total of 1403 patients underwent randomization. The full analysis set comprised 1385 patients (692 in the RIPC group and 693 in the sham-RIPC group). There was no significant between-group difference in the rate of the composite primary end point (99 patients [14.3%] in the RIPC group and 101 [14.6%] in the sham-RIPC group, P = 0.89) or of any of the individual components: death (9 patients [1.3%] and 4 [0.6%], respectively; P = 0.21), myocardial infarction (47 [6.8%] and 63 [9.1%], P = 0.12), stroke (14 [2.0%] and 15 [2.2%], P = 0.79), and acute renal failure (42 [6.1%] and 35 [5.1%], P = 0.45). The results were similar in the per-protocol analysis. No treatment effect was found in any subgroup analysis. No significant differences between the RIPC group and the sham-RIPC group were seen in the level of troponin release, the duration of mechanical ventilation, the length of stay in the intensive care unit or the hospital, new onset of atrial fibrillation, and the incidence of postoperative delirium. No RIPC-related adverse events were observed. CONCLUSIONS Upper-limb RIPC performed while patients were under propofol-induced anesthesia did not show a relevant benefit among patients undergoing elective cardiac surgery.
New England Journal of Medicine 10/2015; 373(15). DOI:10.1056/NEJMoa1413579 · 55.87 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Impaired cardiac repolarization, indicated by prolonged QT interval, may cause critical ventricular arrhythmias. Many anesthetics increase the QT interval by blockade of rapidly acting potassium rectifier channels. Although xenon does not affect these channels in isolated cardiomyocytes, the authors hypothesized that xenon increases the QT interval by direct and/or indirect sympathomimetic effects. Thus, the authors tested the hypothesis that xenon alters the heart rate-corrected cardiac QT (QTc) interval in anesthetic concentrations.
The effect of xenon on the QTc interval was evaluated in eight healthy volunteers and in 35 patients undergoing abdominal or trauma surgery. The QTc interval was recorded on subjects in awake state, after their denitrogenation, and during xenon monoanesthesia (FetXe > 0.65). In patients, the QTc interval was recorded while awake, after anesthesia induction with propofol and remifentanil, and during steady state of xenon/remifentanil anesthesia (FetXe > 0.65). The QTc interval was determined from three consecutive cardiac intervals on electrocardiogram printouts in a blinded manner and corrected with Bazett formula.
In healthy volunteers, xenon did not alter the QTc interval (mean difference: +0.11 ms [95% CI, -22.4 to 22.7]). In patients, after anesthesia induction with propofol/remifentanil, no alteration of QTc interval was noted. After propofol was replaced with xenon, the QTc interval remained unaffected (417 ± 32 ms vs. awake: 414 ± 25 ms) with a mean difference of 4.4 ms (95% CI, -4.6 to 13.5).
Xenon monoanesthesia in healthy volunteers and xenon/remifentanil anesthesia in patients without clinically relevant cardiovascular disease do not increase QTc interval.
[Show abstract][Hide abstract] ABSTRACT: Critically ill patients often require renal replacement therapy accompanied by thrombocytopenia. Thrombocytopenia during heparin anticoagulation may be due to heparin-induced thrombocytopenia with need for alternative anticoagulation. Therefore, we compared argatroban and lepirudin in critically ill surgical patients.
Following institutional review board approval and written informed consent, critically ill surgical patients more than or equal to 18 years with suspected heparin-induced thrombocytopenia, were randomly assigned to receive double-blind argatroban or lepirudin anticoagulation targeting an activated Partial Thromboplastin Time (aPTT) of 1.5 to 2 times baseline. In patients requiring continuous renal replacement therapy we compared the life-time of hemodialysis filters. We evaluated in all patients the incidence of bleeding and thrombembolic events.
We identified 66 patients with suspected heparin-induced thrombocytopenia, including 28 requiring renal replacement therapy. Mean filter lifetimes did not differ between groups (argatroban 32 ± 25 hours (n = 12) versus lepirudin 27 ± 21 hours (n = 16), mean difference 5 hours, 95% CI −13 to 23, P = 0.227). Among all 66 patients, relevant bleeding occurred in four argatroban- versus eleven lepirudin-patients (OR 3.9, 95% CI 1.1 to 14.0, P = 0.040). In the argatroban-group, three thromboembolic events occurred compared to two in the lepirudin group (OR 0.7, 95% CI 0.1 to 4.4, P = 0.639). The incidence of confirmed heparin-induced thrombocytopenia was 23% (n = 15) in our study population.
This first randomized controlled double-blind trial comparing two direct thrombin inhibitors showed comparable effectiveness for renal replacement therapy, but suggests fewer bleeds in surgical patients with argatroban anticoagulation.
Clinical Trials.gov NCT00798525. Registered 25 November 2008
[Show abstract][Hide abstract] ABSTRACT: Background:
Dislocation of epidural catheters (EC) is associated with early termination of regional analgesia and rare complications like epidural bleeding. We tested the hypothesis that maximum effort in fixation by tunneling and suture decreases the incidence of catheter dislocation.
Patients scheduled for major surgery (n = 121) were prospectively randomized in 2 groups. Thoracic EC were subcutaneously tunneled and sutured (tunneled) or fixed with adhesive tape (taped). The difference of EC length at skin surface level immediately after insertion and before removal was determined and the absolute values were averaged. Postoperative pain was evaluated by numeric rating scale twice daily and EC tips were screened microbiologically after removal.
Both groups did not differ with respect to treatment duration (tunneled: 109 hours ± 46, taped: 97 ± 37) and postoperative pain scores. Tunneling significantly reduced average extent (tunneled: 3 mm ± 7, taped: 10 ± 18) and incidence of clinically relevant EC dislocation (>20 mm, tunneled: 1/60, taped: 9/61). Bacterial contamination showed a tendency to be lower in patients with tunneled catheters (8/59, taped: 14/54, P = 0.08).
Thorough fixation of EC by tunneling and suturing decreases the incidence and extent of dislocation and potentially even that of bacterial contamination.
[Show abstract][Hide abstract] ABSTRACT: Background
Electrical impedance tomography (EIT) of the lungs facilitates visualization of ventilation distribution during mechanical ventilation. Its intraoperative use could provide the basis for individual optimization of ventilator settings, especially in patients at risk for ventilation-perfusion mismatch and impaired gas exchange, such as patients undergoing major open upper abdominal surgery. EIT throughout major open upper abdominal surgery could encounter difficulties in belt positioning and signal quality. Thus, we conducted a pilot-study and tested whether EIT is feasible in patients undergoing major open upper abdominal surgery.
Following institutional review board’s approval and written informed consent, we included patients scheduled for major open upper abdominal surgery of at least 3 hours duration. EIT measurements were conducted prior to intubation, at the time of skin incision, then hourly during surgery until shortly prior to extubation and after extubation. Number of successful intraoperative EIT measurements and reasons for failures were documented. From the valid measurements, a functional EIT image of changes in tidal impedance was generated for every time point. Regions of interest were defined as horizontal halves of the picture. Monitoring of ventilation distribution was assessed using the center of ventilation index, and also using the total and dorsal ventilated lung area. All parameter values prior to and post intubation as well as extubation were compared. A p < 0.05 was considered statistically significant.
A total of 120 intraoperative EIT measurements during major abdominal surgery lasting 4-13 hours were planned in 14 patients. The electrode belt was attached between the 2nd and 4th intercostal space. Consecutive valid measurements could be acquired in 13 patients (93%). 111 intraoperative measurements could be retrieved as planned (93%). Main obstacle was the contact of skin electrodes. Despite the high belt position, distribution of tidal volume showed a significant shift of ventilation towards ventral lung regions after intubation. This was reversed after weaning from mechanical ventilation.
Despite a high belt position, monitoring of ventilation distribution is feasible in patients undergoing major open upper abdominal surgery lasting from 4 to 13 hours. Therefore, further interventional trials in order to optimize ventilatory management should be initiated.
[Show abstract][Hide abstract] ABSTRACT: Background and Goal of study: Xenon (Xe) anaesthesia is associated with stable blood pressure and rapid recovery from general anaesthesia. Thus, it appears favourable to apply Xe‐based anaesthesia in patients at cardiovascular risk, e.g., during carotid endarterectomy. However, volatile anaesthetics frequently interfere with routine neuromonitoring, like somatosensory evoked potentials (SSEP). Thus, we test the hypothesis that SSEP amplitude and latency were not altered during Xe anaesthesia in patients prior to carotid endarterectomy.Material and methods: Following IRB‐approval, general anesthesia was induced in 20 unpremedicated patients by intravenous propofol (Prop)/ remifentanil and rocuronium. Patients were intubated and mechanically ventilated (FiO2 0.35) to normocapnia. Invasive arterial pressure, heart rate, and Narcotrend® depth of anaesthesia were continuously recorded. Arterial pressure was maintained by titration of intravenous norepinephrine. Median nerve SSEP amplitudes and latencies were repeatedly assessed over both hemispheres. Following recording of reference values during Prop, Xe was administered targeting end‐tidal 60% in oxygen. Values during Xe were compared to Prop prior to surgical stimulation. Statistics: Mean ±SD, Student's t‐test, P< 0.05.Results and Discussion: Mean arterial pressure (Prop 91 mmHg ±15; Xe 93±10), heart rate (Prop 57 min‐1 ±12; Xe 54±13), and anesthetic depth (Prop 38±6; Xe 38±6) did not differ between groups. Intravenous norepinephrine demand was significant larger during Prop (Prop: 0.067 μg kg‐1 min‐1 ± 0.042 Xe: 0,028 ± 0.021; P< 0.001). SSEP amplitudes were decreased by Xe (Prop: 3.6 μV ±1.7; Xe: 1.4±0.7; P< 0.001), while SSEP latencies were not altered (Prop: 22.9 ms ±2; Xe: 22.6±2.9; P=0.49) A too low SSEP amplitude during Xe anaesthesia rendered SSEP monitoring impossible in one case, which had a baseline amplitude during Prop below 0.5 μV.Conclusion: Anaesthetic concentrations of Xe decrease SSEP amplitude to 43 percent of baseline while SSEP latencies remain unaltered, thus preserving the value of SSEP monitoring as a tool for guiding surgical strategy.
[Show abstract][Hide abstract] ABSTRACT: Pre-hospital hypotension in trauma patients is associated with high mortality. Especially for patients with severe traumatic brain injury (TBI), arterial normotension or even hypertension (AHT) is considered an important mechanism for sustaining adequate cerebral perfusion pressure. The effect of pre-hospital arterial hypertension (pAHT) on in-hospital mortality after trauma has not been studied to date.
We retrospectively analyzed data in the trauma registry of the German Society for Trauma Surgery (DGU) on all trauma patients in Germany from 1993 to 2008 who were 16 to 80 years old at the time of the trauma and had an injury severity score (ISS) of 9 or above (total, 42 500 patient data sets). For the analysis, we divided the patients into two groups: those with and those without TBI. We further divided the TBI patients into five subgroups depending on the course of their systolic blood pressure up to the moment of their arrival at the hospital. We also analyzed the patients' demographic data, patterns of injury, and accident mechanisms.
Trauma patients with TBI and pAHT (142 of 561 patients) had a significantly higher mortality than normotensive TBI patients (25.3% vs. 13.5%, p<0.001). Arterial hypertension that either rises or falls before the patient reaches the hospital is associated with higher in-hospital mortality. A logistical regression analysis of 5384 patients revealed that patients with pAHT (n = 561) had an odds ratio of 1.9 (95% confidence interval, 1.4 to 1.6) for death in the hospital compared to normotensive patients (n = 6020).
Systolic blood pressure values above 160 mm Hg before arrival in the hospital worsen the outcome of trauma patients with TBI.
Deutsches Ärzteblatt International 12/2012; 109(49):849-56. DOI:10.3238/arztebl.2012.0849 · 3.52 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: BACKGROUND: Strategies to protect the brain from postoperative delirium (POD) after hip fracture are urgently needed. The development of delirium often is associated with the loss of independence, poor functional recovery, and increased morbidity, as well as increases in length of hospital stay, discharges to nursing facilities, and healthcare costs. We hypothesize that xenon may reduce the burden of POD, (i) by avoiding the need to provide anesthesia with a drug that targets the gamma-amino-butyric acid (GABA)A receptor and (ii) through beneficial anesthetic and organ-protective effects.Methods and designAn international, multicenter, phase 2, prospective, randomized, blinded, parallel group and controlled trial to evaluate the incidence of POD, diagnosed with the Confusion Assessment Method (CAM), in older patients undergoing hip fracture surgery under general anesthesia with xenon or sevoflurane, for a period of 4 days post surgery (primary outcome) is planned. Secondary objectives are to compare the incidence of POD between xenon and sevoflurane, to evaluate the incidence of POD from day 5 post surgery until discharge from hospital, to determine the time to first POD diagnosis, to evaluate the duration of POD, to evaluate the evolution of the physiological status of the patients in the postoperative period, to evaluate the recovery parameters, to collect preliminary data to evaluate the economical impact of POD in the postoperative period and to collect safety data. Patients are eligible if they are older aged (>= 75 years) and assigned to a planned hip fracture surgery within 48 h after the hip fracture. Furthermore, patients need to be willing and able to complete the requirements of this study including the signature of the written informed consent. A total of 256 randomized patients in the 10 participating centers will be recruited, that is, 128 randomized patients in each of the 2 study groups (receiving either xenon or sevoflurane).Trial registrationEudraCT Identifier: 2009-017153-35; ClinicalTrials.gov Identifier: NCT01199276.
[Show abstract][Hide abstract] ABSTRACT: Background
Intraoperative hypotension is associated with increased risk of perioperative complications. The N-methyl-d-aspartate (NMDA) receptor (NMDA-R) antagonist xenon (Xe) induces general anaesthesia without impairment of cardiac output and vascular resistance. Mechanisms involved in cardiovascular stability have not been identified.Methods
Muscle sympathetic activity (MSA) (microneurography), sympathetic baroreflex gain, norepinephrine (NE) plasma concentration (high-performance liquid chromatography), anaesthetic depth (Narcotrend® EEG monitoring), and vital parameters were analysed in vivo during Xe mono-anaesthesia in human volunteers (n8). In vitro, NE transporter (NET) expressing HEK293 cells and SH-SY5Y neuroblastoma cells were pre-treated with ketamine, MK-801, NMDA/glycine, or vehicle. Subsequently, cells were incubated with or without Xe (65). NE uptake was measured by using a fluorescent NET substrate (n4) or [3H]NE (n6).ResultsIn vivo, Xe anaesthesia increased mean (standard deviation) arterial pressure from 93 (4) to 107 (6) mm Hg and NE plasma concentration from 156 (55) to 292 (106) pg ml -1, P<0.01. MSA and baroreflex gain were unaltered. In vitro, ketamine decreased NET activity (P<0.01) in NET-expressing HEK293 cells, while Xe, MK-801, and NMDA/glycine did not. Xe reduced uptake in SH-SY5Y cells expressing NET and NMDA-Rs (P<0.01). MK-801 (P<0.01) and ketamine (P<0.01) also reduced NET activity, but NMDA/glycine blocked the effect of Xe on [3H]NE uptake.Conclusions
In vivo, Xe anaesthesia does not alter sympathetic activity and baroreflex gain, despite increased mean arterial pressure. In vitro, Xe decreases the uptake of NE in neuronal cells by the inhibition of NET. This inhibition might be related to NMDA-R antagonism and explain increased NE concentrations at the synaptic cleft and in plasma, contributing to cardiovascular stability during Xe anaesthesia.
BJA British Journal of Anaesthesia 09/2012; 109(6). DOI:10.1093/bja/aes303 · 4.85 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Prolonged postoperative decrease in lung function is common after major upper abdominal surgery. Evidence suggests that ventilation with low tidal volumes may limit the damage during mechanical ventilation. We compared postoperative lung function of patients undergoing upper abdominal surgery, mechanically ventilated with high or low tidal volumes.
This was a double-blind, prospective, randomized controlled clinical trial. One hundred and one patients (age ≥ 50 yr, ASA ≥ II, duration of surgery ≥ 3 h) were ventilated with: (i) high [12 ml kg(-1) predicted body weight (PBW)] or (ii) low (6 ml kg(-1) PBW) tidal volumes intraoperatively. The positive end-expiratory pressure was 5 cm H(2)O in both groups and breathing frequency adjusted to normocapnia. Time-weighted averages (TWAs) of forced vital capacity (FVC) and forced expiratory volume in 1 s (FEV(1)) until 120 h after operation were compared (P<0.025 considered statistically significant). Secondary outcomes were oxygenation, respiratory and non-respiratory complications, length of stay and mortality.
The mean (sd) values of TWAs of FVC and FEV(1) were similar in both groups: FVC: 6 ml group 1.8 (0.7) litre vs 12 ml group 1.6 (0.5) litre (P=0.12); FEV(1): 6 ml group 1.4 (0.5) litre vs 12 ml group 1.2 (0.4) litre (P=0.15). FVC and FEV(1) at any single time point and secondary outcomes did not differ significantly between groups.
Prolonged impaired lung function after major abdominal surgery is not ameliorated by low tidal volume ventilation.
BJA British Journal of Anaesthesia 06/2012; 109(2):263-71. DOI:10.1093/bja/aes140 · 4.85 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Desmopressin (DDAVP) and fibrinogen improve platelet function and clot stability. We investigated the influence of DDAVP and fibrinogen on whole blood coagulation in an in vitro model of hypothermia and acidosis.
After IRB approval and written consent blood samples were taken from 10 healthy volunteers. Samples were prepared with hydrochloric acid to maintain--beside normal pH--reduced pH (∼7.2) and severely reduced pH (∼7.0), and were assigned to four treatment groups: addition of either isotonic saline for compensation of dilutional effects (ISO), desmopressin (DDAVP+), fibrinogen (FIB+), or both substances (DDAVP+FIB+). Baseline was ISO at 37°C and normal pH. Remaining samples were incubated for 30 min and measured at 32°. Rotation thrombelastometry (ROTEM) after extrinsically activation and fibrin polymerization was tested. Repeated measures ANOVA were performed (p < 0.05).
Hypothermia and acidosis synergistically impaired whole blood coagulation. DDAVP+ normalized maximum clot firmness (MCF) at normal pH. Coagulation time (CT) was not affected. FIB+ normalized MCF at pH 7.35 and pH 7.2. CT was normalized independently of pH. DDAVP+FIB+ did not show additional effects to FIB+. Fibrin polymerization was increased by FIB+ and DDAVP+FIB+ independently of pH. DDAVP+ did not alter fibrin polymerization.
DDAVP and fibrinogen increased whole blood coagulation under hypothermia. Acidosis diminished this effect. Thus, acidosis should be corrected first and then both substances could be used for bridging until normothermia can be achieved. In combination, the effects of fibrinogen were overwhelming DDAVP effects. Thus, combined administration did not show any benefit compared to fibrinogen administration alone.
Scandinavian journal of clinical and laboratory investigation 07/2011; 71(4):292-8. DOI:10.3109/00365513.2011.561870 · 1.90 Impact Factor