Jens Scholz

Multicenter Randomized Comparison of the Efficacy and Safety of Xenon and Isoflurane in Patients Undergoing Elective Surgery

Background All general anesthetics used are known to have a negative inotropic side effect. Since xenon does not have a negative inotropic effect, it could be an interesting future general anesthetic. The aim of this clinical multicenter trial was to test the hypothesis of whether recovery after xenon anesthesia is faster compared with an accepted, standardized anesthetic regimen and that it is as effective and safe. Method A total of 224 patients in six centers were included in the protocol. They were randomly assigned to receive either xenon (60 ± 5%) in oxygen or isoflurane (end-tidal concentration, 0.5%) combined with nitrous oxide (60 ± 5%). Sufentanil (10 &mgr;g) was intravenously injected if indicated by defined criteria. Hemodynamic, respiratory, and recovery parameters, the amount of sufentanil, and side effects were assessed. Results The recovery parameters demonstrated a statistically significant faster recovery from xenon anesthesia when compared with isoflurane–nitrous oxide. The additional amount of sufentanil did not differ between both anesthesia regimens. Hemodynamics and respiratory parameters remained stable throughout administration of both anesthesia regimens, with advantages for the xenon group. Side effects occurred to the same extent with xenon in oxygen and isoflurane–nitrous oxide. Conclusion This first randomized controlled multicenter trial on the use of xenon as an inhalational anesthetic confirms, in a large group of patients, that xenon in oxygen provides effective and safe anesthesia, with the advantage of a more rapid recovery when compared with anesthesia using isoflurane–nitrous oxide.

Evidence for Susceptibility to Malignant Hyperthermia in Patients with Exercise-induced Rhabdomyolysis

BackgroundMalignant hyperthermia (MH), heat stroke, and exercise-induced rhabdomyolysis (ER) were suspected to be related syndromes. However, it is not known whether individuals with history of ER have an increased incidence of susceptibility to MH. To establish an association between ER and susceptibility to MH, the authors determined the MH status in patients with a history of MH-like episodes induced by physical stress. MethodsTwelve unrelated patients with ER, 18 patients with anesthesia-induced MH, and 28 controls were investigated with the in vitro contracture test (IVCT) according to the European MH Group protocol and the ryanodine contracture test. In addition, all patients were screened for genetic mutations, and histology was performed on muscle specimens. ResultsTen ER patients had positive IVCT results, one patient had a negative test result, and one patient showed equivocal responses. Samples from patients with positive IVCT results showed pronounced contractures after exposition to ryanodine, as opposed to specimens from patients with negative IVCT results, which developed contractures slowly. Three ER patients had mutations at the ryanodine receptor gene. All anesthesia-induced MH patients had positive IVCT results, two of them presented the C1840T mutation. The control patients had normal contracture test results and no typical MH mutations. Histologic examination determined no specific myopathies in any patient. ConclusionsRegarding these results, the authors recommend performing muscle biopsies for histologic examination and IVCT in patients with ER. In addition, the patient should be seen by a neurologist and screened for genetic abnormalities to shed light on the genetics of MH.

Overlapping induction of anesthesia: an analysis of benefits and costs.

Background:Overlapping induction (OI), i.e., induction of anesthesia with an additional team while the previous patient is still in the operating room (OR), was investigated. Methods:The study period was 60 days in two followed by three ORs during surgical Block Time (7:30 am until 3:00 pm). Patients were admitted the day before surgery and were thus available and did not have surgery that day unless there was a time reduction. Facilities were already constructed. Number of cases, Nonsurgical Time (Skin Suture Finish until next Procedure Start Time), Turnover Time, and Anesthesia Control Time plus Turnover Time were studied. In addition, economic benefit was calculated. Results:Three hundred thirty-five cases were studied. Using OI, the time of care of regularly scheduled cases was shortened, and the number of cases performed within OR Block Time increased (151 to 184 cases; P < 0.05). Nonsurgical Time (in h:min) decreased (1:08 ± 0:26 to 0:57 ± 0:18; P < 0.001), Turnover Time decreased (0:38 ± 0:24 to 0:25 ± 0:15; P < 0.05), and Anesthesia Control Time plus Turnover Time decreased (0:43 ± 0:23 to 0:28 ± 0:18; P < 0.001). Subgroup analysis showed a significant benefit of OI only in three ORs. In three ORs, economic benefit can be gained at a case mix index greater than 0.3 besides additional costs. Conclusions:Overlapping induction increased productivity and profit despite the expense of additional staff. Subgroup analysis emphasizes the importance of the number of ORs involved in OI.

Reversal of rocuronium-induced neuromuscular blockade with sugammadex compared with neostigmine during sevoflurane anaesthesia: results of a randomised, controlled trial

Background and objective Sugammadex, a modified γ-cyclodextrin, is a selective relaxant-binding agent designed to reverse the effects of the steroidal neuromuscular blocking agents rocuronium or vecuronium. This study compared the efficacy of sugammadex and neostigmine for reversal of neuromuscular blockade induced by rocuronium for facilitating elective surgery. Methods This randomised, multicentre, parallel-group trial included 98 adult patients. Patients received intravenous propofol for induction followed by sevoflurane maintenance anaesthesia. Neuromuscular blockade was monitored using acceleromyography and a train-of-four (TOF) mode of stimulation. Patients were randomly allocated to receive sugammadex 2.0 mg kg−1 or neostigmine 50 μg kg−1 (with glycopyrrolate 10 μg kg−1) at reappearance of the second response of the TOF (mean 16% twitch height of first response) after the last dose of rocuronium. Safety was evaluated by assessing adverse events, laboratory variables and vital signs. Results Time to recovery of the TOF ratio of 0.9 after sugammadex compared with neostigmine was significantly shorter (P < 0.0001), being 1.5 versus 18.6 min (geometric means). Predictability of response was greater with sugammadex than neostigmine: with 98% of sugammadex patients versus 11% of neostigmine patients recovering to a TOF ratio of 0.9 within 5 min. There were no clinical events related to residual neuromuscular blockade or reoccurrence of blockade. Serious adverse events were observed in two sugammadex-treated patients and in three neostigmine-treated patients, respectively, but none were considered related to study drugs. Conclusion Sugammadex achieved significantly faster recovery of neuromuscular function after rocuronium to a TOF ratio of 0.9 compared with neostigmine (Clinicaltrials.gov identifier: NCT00451217).

Evidence and consensus-based German guidelines for the management of analgesia, sedation and delirium in intensive care--short version.

Targeted monitoring of analgesia, sedation and delirium, as well as their appropriate management in critically ill patients is a standard of care in intensive care medicine. With the undisputed advantages of goal-oriented therapy established, there was a need to develop our own guidelines on analgesia and sedation in intensive care in Germany and these were published as 2nd Generation Guidelines in 2005. Through the dissemination of these guidelines in 2006, use of monitoring was shown to have improved from 8 to 51% and the use of protocol-based approaches increased to 46% (from 21%). Between 2006–2009, the existing guidelines from the DGAI (Deutsche Gesellschaft für Anästhesiologie und Intensivmedizin) and DIVI (Deutsche Interdisziplinäre Vereinigung für Intensiv- und Notfallmedizin) were developed into 3rd Generation Guidelines for the securing and optimization of quality of analgesia, sedation and delirium management in the intensive care unit (ICU). In collaboration with another 10 professional societies, the literature has been reviewed using the criteria of the Oxford Center of Evidence Based Medicine. Using data from 671 reference works, text, diagrams and recommendations were drawn up. In the recommendations, Grade “A” (very strong recommendation), Grade “B” (strong recommendation) and Grade “0” (open recommendation) were agreed. As a result of this process we now have an interdisciplinary and consensus-based set of 3rd Generation Guidelines that take into account all critically illness patient populations. The use of protocols for analgesia, sedation and treatment of delirium are repeatedly demonstrated. These guidelines offer treatment recommendations for the ICU team. The implementation of scores and protocols into routine ICU practice is necessary for their success.

Neuroendocrine stress response and heart rate variability: a comparison of total intravenous versus balanced anesthesia.

Attenuating intraoperative stress is a key factor in improving outcome. We compared neuroendocrine changes and heart rate variability (HRV) during balanced anesthesia (BAL) versus total IV anesthesia (TIVA). Forty-three patients randomly received either BAL (sevoflurane/remifentanil) or TIVA (propofol/remifentanil). Depth of anesthesia was monitored by bispectral index. Stress hormones were measured at 7 time points (P1 = baseline; P2 = tracheal intubation; P3 = skin incision; P4 = maximum operative trauma; P5 = end of surgery; P6 = tracheal extubation; P7 = 15 min after tracheal extubation). HRV was analyzed by power spectrum analysis: very low frequency (VLF), low frequency (LF), high frequency (HF), LF/HF ratio, and total power (TP). LF/HF was higher in TIVA at P6 and TP was higher in TIVA at P3–7 (P3: 412.6 versus 94.2; P4: 266.7 versus 114.6; P5: 290.3 versus 111.9; P6: 1523.7 versus 658.1; P7: 1225.6 versus 342.6 ms2). BAL showed higher levels of epinephrine (P7: 100.5 versus 54 pg/mL), norepinephrine (P3: 221 versus 119.5; P4: 194 versus 130.5 pg/mL), adrenocorticotropic hormone (P2 10.5 versus 7.7; P5: 5.3 versus 3.6; P6: 10.9 versus 5.3; P7: 20.5 versus 7.1 pg/mL) and cortisol (P7: 6.9 versus 3.9 &mgr;g/dL). This indicates a higher sympathetic outflow using BAL versus TIVA during ear-nose-throat surgery.

Sevoflurane but not propofol preserves myocardial function during minimally invasive direct coronary artery bypass surgery.

Volatile anesthetics exert cardioprotective properties in experimental and clinical studies. We designed this study to investigate the effects of sevoflurane on left ventricular (LV) performance during minimally invasive direct coronary artery bypass grafting (MIDCAB) without cardiopulmonary bypass. Fifty-two patients scheduled for MIDCAB surgery were randomly assigned to a propofol or a sevoflurane group. Apart from the anesthetics used, there was no difference in surgical and anesthetic management. After determination of cardiac troponin T, creatine kinase, and creatine kinase MB, electrocardiographic (ECG) data and echocardiography variables (myocardial performance index and early to atrial filling velocity ratio) the left anterior descending coronary artery (LAD) was clamped until anastomosis with the left internal mammary artery was completed. During LAD occlusion and during reperfusion, echocardiography measurements were repeated. Blood samples were obtained repeatedly for up to 72 h. After LAD occlusion, myocardial performance index and early to atrial filling velocity ratio in the propofol group deteriorated significantly from 0.40 ± 0.12 and 1.29 ± 0.35 to 0.49 ± 0.10 and 1.13 ± 0.22, respectively, whereas there was no change in the sevoflurane group. In the propofol group myocardial performance index remained increased (0.47 ± 0.11) compared with baseline during reperfusion. There were no significant differences in ECG and laboratory values between groups. In conclusion, during a brief period of ischemia in patients undergoing MIDCAB surgery, sevoflurane preserved myocardial function better than propofol.

Management of the predicted difficult airway: a comparison of conventional blade laryngoscopy with video-assisted blade laryngoscopy and the GlideScope

Background and objective We investigated whether the use of two different video laryngoscopes [direct-coupled interface (DCI) video laryngoscope and GlideScope] may improve laryngoscopic view and intubation success compared with the conventional direct Macintosh laryngoscope (direct laryngoscopy) in patients with a predicted difficult airway. Methods One hundred and twenty adult patients undergoing elective minor surgery requiring general anaesthesia and endotracheal intubation presenting with at least one predictor for a difficult airway were enrolled after Institutional Review Board approval and written informed consent was obtained. Repeated laryngoscopy was performed using direct laryngoscope, DCI laryngoscope and GlideScope in a randomized sequence before patients were intubated. Results Both video laryngoscopes showed significantly better laryngoscopic view (according to Cormack and Lehane classification as modified by Yentis and Lee = C&L) than direct laryngoscope. Laryngoscopic view C&L ≥ III was measured in 30% of patients when using direct laryngoscopy, and in only 11% when using the DCI laryngoscope (P < 0.001). The GlideScope enabled significantly better laryngoscopic view (C&L ≥ III: 1.6%) than both direct (P < 0.001) and DCI laryngoscopes (P < 0.05). Clinically relevant improvement in the specific 36 patients with insufficient direct view (C&L ≥ III) could be achieved significantly more often with the GlideScope (94.4%) than with the DCI laryngoscope (63.8%; P < 0.01). Laryngoscopy time did not differ between instruments [median (range): direct laryngoscope, 13 (5–33) s; DCI laryngoscope, 14 (6–40) s; GlideScope, 13 (5–34) s]. In contrast, tracheal intubation needed significantly more time with both video laryngoscopes [DCI laryngoscope, 27 (17–94) s, P < 0.05 and GlideScope, 33 (18–68) s, P < 0.01] than with the direct laryngoscope [22.5 (12–49) s]. Intubation failed in four cases (10%) using the direct laryngoscope and in one case (2.5%) each using the DCI laryngoscope and the GlideScope. Conclusion We conclude that the video laryngoscope and GlideScope in particular may be useful instruments in the management of the predicted difficult airway.

Heart Rate Variability Predicts Severe Hypotension after Spinal Anesthesia for Elective Cesarean Delivery

Background:Hypotension due to vasodilation during subarachnoid block (SAB) for elective cesarean delivery may be harmful. Heart rate variability (HRV), reflecting autonomic control, may identify patients at risk of hypotension. Methods:Retrospectively, HRV was analyzed in 41 patients who were classified into one of three groups depending on the decrease in systolic blood pressure (SBP): mild (SBP > 100 mmHg), moderate (100 > SBP > 80 mmHg), or severe (SBP < 80 mmHg). Prospectively, HRV and hemodynamic data of 19 patients were studied. Relative low frequency (LF), relative high frequency (HF), and LF/HF ratio were analyzed. Results:Retrospective analysis of HRV showed a significantly higher sympathetic and lower parasympathetic drive in the groups with moderate and severe compared with mild hypotension before SAB (median, 25th/75th percentiles): LF/HF: mild: 1.2 (0.9/1.8), moderate: 2.8 (1.8/4.6), P < 0.05 versus mild; severe: 2.7 (2.0/3.5), P < 0.05 versus mild. Results were confirmed by findings of LF and HF. Prospectively, patients were grouped according to LF/HF before SAB: low-LF/HF: 1.5 (1.1/2.0) versus high-LF/HF: 4.0 (2.8/4.7), P < 0.05; low-LF: 58 ± 9% versus high-LF: 75 ± 10%, P < 0.05; low-HF: 41 ± 10% versus high-HF: 25 ± 10%, P < 0.05. High-risk patients had a significantly lower SBP after SAB (76 ± 21 vs. 111 ± 12 mmHg; P < 0.05). Conclusions:Retrospectively analyzed HRV of patients scheduled to undergo elective cesarean delivery during SAB showed significant differences depending on the severity of hypotension after SAB. Preliminary findings were prospectively confirmed. High LF/HF before SAB predicted severe hypotension. Preoperative HRV analysis may detect patients at risk of hypotension after SAB.

A Phase III, Double-blind, Placebo-controlled, Multicenter Study on the Efficacy of Recombinant Human Antithrombin in Heparin-resistant Patients Scheduled to Undergo Cardiac Surgery Necessitating Cardiopulmonary Bypass

Background:The study evaluated the efficacy of recombinant human antithrombin (rhAT) for restoring heparin responsiveness in heparin resistant patients undergoing cardiac surgery. Methods:This was a multicenter, randomized, double-blind, placebo-controlled study in heparin-resistant patients undergoing cardiac surgery with cardiopulmonary bypass. Heparin resistance was diagnosed when the activated clotting time was less than 480 s after 400 U/kg heparin. Fifty-four heparin-resistant patients were randomized. One cohort received 75 U/kg rhAT, and the other received normal saline. If the activated clotting time remained less than 480 s, this was considered treatment failure, and 2 units fresh frozen plasma was transfused. Patients were monitored for adverse events. Results:Only 19% of patients in the rhAT group received fresh frozen plasma, compared with 81% of patients in the placebo group (P < 0.001). During their hospitalization, 48% of patients in the rhAT group received fresh frozen plasma, compared with 85% of patients in the placebo group (P = 0.009). Patients in the placebo group required higher heparin doses (P < 0.005) for anticoagulation. There was no increase in serious adverse events associated with rhAT. There was increased blood loss 12 h postoperatively (P = 0.05) with a trend toward increased 24-h bleeding in the rhAT group (P = 0.06). There was no difference between the groups in blood and platelet transfusions. Conclusion:Treatment with 75 U/kg rhAT is effective in restoring heparin responsiveness and promoting therapeutic anticoagulation in the majority of heparin-resistant patients. Treating heparin-resistant patients with rhAT may decrease the requirement for heparin and fresh frozen plasma.