Papers by Walter Klimscha
psychopraxis. neuropraxis, 2020
Die Anti-NMDA(N-Methyl-D-Aspartat)-Rezeptor-Enzephalitis ist eine seltene autoimmunologisch bedin... more Die Anti-NMDA(N-Methyl-D-Aspartat)-Rezeptor-Enzephalitis ist eine seltene autoimmunologisch bedingte Erkrankung mit verschiedenen neuropsychiatrischen Symptomen, die durch den Nachweis von NMDA-Rezeptor-Antikörpern im Liquor diagnostiziert wird. Die gängigen Behandlungsprotokolle beinhalten ein Stufenschema der Immuntherapien; allerdings beruhen die therapeutischen Entscheidungen derzeit auf einem Grad-IV-Evidenzniveau. Wir berichten hier über zwei junge, unterschiedlich betroffene Patientinnen und beschreiben die Therapiestrategien inklusive der Kombination verschiedener Immuntherapien einschließlich Ocrelizumab und Überlegungen bezüglich Fertilitätserhalt. Anti-NMDA (N-methyl-D-aspartate) receptor encephalitis is a rare autoimmune-mediated disease characterised by various neuropsychiatric symptoms and diagnosed by the presence of NMDA receptor antibodies in the cerebral spinal fluid. Treatment protocols commonly include a stepwise escalation of immunotherapies, but decisions are currently based on level IV evidence. Here, we report on two young women affected to different degrees and we describe the therapeutic strategies including the combination of several immunotherapies, including ocrelizumab, and considerations regarding the preservation of fertility.
The Lancet. Respiratory medicine, May 28, 2017
Little is known about the incidence of severe critical events in children undergoing general anae... more Little is known about the incidence of severe critical events in children undergoing general anaesthesia in Europe. We aimed to identify the incidence, nature, and outcome of severe critical events in children undergoing anaesthesia, and the associated potential risk factors. The APRICOT study was a prospective observational multicentre cohort study of children from birth to 15 years of age undergoing elective or urgent anaesthesia for diagnostic or surgical procedures. Children were eligible for inclusion during a 2-week period determined prospectively by each centre. There were 261 participating centres across 33 European countries. The primary endpoint was the occurence of perioperative severe critical events requiring immediate intervention. A severe critical event was defined as the occurrence of respiratory, cardiac, allergic, or neurological complications requiring immediate intervention and that led (or could have led) to major disability or death. This study is registered w...
Canadian Journal of Anesthesia/Journal canadien d'anesthésie, 2016
Background The intravenous anesthetic propofol is a gamma-aminobutyric acid A receptor agonist. P... more Background The intravenous anesthetic propofol is a gamma-aminobutyric acid A receptor agonist. Propofol promotes analgesia by depressing nociceptive transmission in peripheral neurons, antagonizing N-methyl-D-aspartate receptors, and activating gamma-aminobutyric acid A receptors in dorsal root ganglion receptor cells. Nevertheless, it remains unclear whether intraoperative propofol causes clinically meaningful postoperative analgesia. We therefore tested the hypothesis that patients anesthetized with sevoflurane require a greater quantity of postoperative opioids (from the end of surgery until the next postoperative morning) than those anesthetized with propofol. Methods With Institutional Review Board and EudraCT Number approval (2009-011038-82) and patients' informed consent, ninety patients scheduled for open vein stripping were randomized to either sevoflurane or propofol anesthesia at the Medical University of Vienna General Hospital and the Danube Hospital, the largest regional hospital in Vienna. Pain was treated with bolus piritramide and patient-controlled morphine hydrochloride. The primary outcome was total opioid use from the end of surgery until the first postoperative morning. For the initial four postoperative hours and on the first postoperative morning, a blinded investigator recorded pain scores on an 11-point Likert verbal response scale. Results The median [interquartile range] morphine sulfate equivalents were 9.8 [4-19] mg in the sevoflurane group and 10 [6-20] mg in the propofol group. Sevoflurane was not superior to propofol on postoperative opioid consumption, giving a ratio of means of 0.91 (95% interimadjusted confidence interval [CI], 0.33 to 2.45; P = 0.74). Additionally, no difference in pain scores was found over time between the two groups, with a mean difference on an 11-point scale of 0.20 (95% interim-adjusted CI,-0.36 to 0.73; P = 0.31). Conclusion Intraoperative sevoflurane did not reduce postoperative analgesia. This finding is consistent with the results in most previous reports. This trial was registered at ClinicalTrials.gov: NCT00712517. Résumé Contexte Le propofol, un anesthésique administré par voie intraveineuse, est un agoniste des récepteurs de l'acide gamma-aminobutyrique A (GABA-A). Le propofol favorise l'analgésie en réduisant la transmission de la
Anesthesiology, 2014
Background: Previous studies show a prolongation of activated partial thromboplastin time and pro... more Background: Previous studies show a prolongation of activated partial thromboplastin time and prothrombin time in healthy volunteers after treatment with sugammadex. The authors investigated the effect of sugammadex on postsurgical bleeding and coagulation variables. Methods: This randomized, double-blind trial enrolled patients receiving thromboprophylaxis and undergoing hip or knee joint replacement or hip fracture surgery. Patients received sugammadex 4 mg/kg or usual care (neostigmine or spontaneous recovery) for reversal of rocuronium- or vecuronium-induced neuromuscular blockade. The Cochran–Mantel–Haenszel method, stratified by thromboprophylaxis and renal status, was used to estimate relative risk and 95% confidence interval (CI) of bleeding events with sugammadex versus usual care. Safety was further evaluated by prespecified endpoints and adverse event reporting. Results: Of 1,198 patients randomized, 1,184 were treated (sugammadex n = 596, usual care n = 588). Bleeding ev...
Pharmacological Research, 1997
The antinociceptive and motor effects of the hydrophilic α2-adrenoceptor agonist ST-91 were studi... more The antinociceptive and motor effects of the hydrophilic α2-adrenoceptor agonist ST-91 were studied after intrathecal administration to male Wistar rats in different heat–pain tests and different test settings. Intrathecal administration of ST-91 caused a dose-dependent increase in hind paw licking latency in the hot-plate test, while in contrast with morphine it had a much lower efficacy in the tail-flick test
The Journal of Thoracic and Cardiovascular Surgery, 2007
Objective: Minimally invasive pectus excavatum repair is a common and painful surgical procedure ... more Objective: Minimally invasive pectus excavatum repair is a common and painful surgical procedure in children and adolescents. Adequate postoperative pain therapy is important far beyond the immediate postoperative period because sensitization to painful stimuli can cause chronic pain or higher pain levels during subsequent surgical procedures. Although data in adults favor thoracic epidural anesthesia for pain control in thoracotomy, data for adolescents and children are scarce. We tested the hypothesis that pain relief with thoracic epidural analgesia was superior to that with intravenous patient-controlled analgesia after minimally invasive pectus excavatum repair in children and adolescents. Methods: We performed a prospective randomized trial with adolescents who had undergone minimally invasive pectus excavatum repair to compare postoperative pain using two different postoperative pain therapy settings: intravenous patientcontrolled analgesia (n ϭ 20) with morphine versus continuous thoracic epidural analgesia (n ϭ 20) with 0.2% ropivacain containing 2 g/mL fentanyl.
The Journal of Thoracic and Cardiovascular Surgery, 2002
Objectives: It has been proved in human subjects and animals that atelectasis is a major cause of... more Objectives: It has been proved in human subjects and animals that atelectasis is a major cause of intrapulmonary shunting and hypoxemia after cardiopulmonary bypass. Animal studies suggest that shunting can be prevented entirely by a total vital capacity maneuver performed before termination of bypass. This study aimed to test this theory in human subjects and to evaluate possible advantages of off-pump coronary artery bypass grafting. Methods: Twenty-four patients scheduled for coronary artery bypass grafting were randomly assigned to receive no total vital capacity maneuver (control group, n ϭ 12) or standard total vital capacity maneuvers (TVCM group, n ϭ 12). Additionally, 12 consecutive patients undergoing off-pump coronary artery bypass grafting (offpump group) were studied. Systemic and central hemodynamics, the pattern of breathing, and ventilatory mechanics were evaluated after induction of anesthesia, after sternotomy, after cardiopulmonary bypass and skin closure, and 4 hours after extubation. Results: The use of total vital capacity maneuvers reduced (P Ͻ .05) intrapulmonary shunting after termination of cardiopulmonary bypass. However, shunting increased (P Ͻ .05) in all groups (control group, 8.2% Ϯ 3.3% vs 25.6% Ϯ 8.1%; TVCM group, 8.7% Ϯ 3.4% vs 24.4% Ϯ 8.5%; and off-pump group, 7.8% Ϯ 2.8% vs 14.0% Ϯ 5.3%) after extubation, but the increase was significantly (P Ͻ .05) less pronounced in the off-pump group. Furthermore, pulmonary compliance decreased (P Ͻ .05) in all groups except the off-pump group after extubation. Duration of hospital and intensive care unit stay was significantly shorter (P Ͻ .05) in the off-pump group than in the other groups. Conclusion: The development of intrapulmonary shunting and hypoxemia after coronary artery bypass grafting can be substantially reduced by performance of total vital capacity maneuvers while patients are mechanically ventilated. However, off-pump coronary artery bypass surgery is superior in preventing shunting and hypoxemia after bypass grafting in the immediate and early postoperative periods, probably leading to substantially shorter intensive care unit and hospital stays.
European Journal of Pharmacology, 1999
Agmatine, an endogenous ligand, interacts both with the a-adrenoceptors and with the imidazoline ... more Agmatine, an endogenous ligand, interacts both with the a-adrenoceptors and with the imidazoline binding sites. The effect of 2 intrathecally administered agmatine on carrageenan-induced thermal hyperalgesia was investigated by means of a paw-withdrawal test in rats. The effect of agmatine on morphine-induced anti-hyperalgesia was also studied. Intrathecal agmatine in doses larger than 250 mg caused a decrease in the pain threshold, with vocalization and agitation lasting for several hours in all animals. Agmatine alone at 1-100 mg did not give rise to any change in the thermal withdrawal threshold in the contralateral non-inflamed paw. Agmatine pretreatment was found to dose-dependently attenuate the thermal hyperalgesia induced by intraplantar carrageenan. The effect of 100 mg agmatine was completely lost by 60 min, whereas the effect of 50 mg was of similar magnitude but exhibited a longer duration. Agmatine posttreatment Ž. Ž. had a slighter effect. Agmatine pretreatment 100 mg together with 1 mg morphine subeffective dose has significantly higher anti-hyperalgesic effect then the individual compounds by themselves. These are the first data demonstrating the behavioral and anti-hyperalgesic effects of intrathecal agmatine. The results reveal important interactions between intrathecal agmatine and opioids in thermal hyperalgesia.
European Journal of Pharmacology, 2002
Kynurenic acid as an endogenous ligand antagonizes all types of ionotropic glutamate receptors, w... more Kynurenic acid as an endogenous ligand antagonizes all types of ionotropic glutamate receptors, with preferential affinity for the glycine-binding site of the N-methyl-D-aspartate (NMDA) receptor. The purpose of the present study was to investigate the antinociceptive potency of continuously administered kynurenic acid on carrageenan-induced thermal hyperalgesia by means of a paw withdrawal test in awake rats. The possible interaction between kynurenic acid and the endogenous mu-opioid receptor agonist peptide, endomorphin-1, was examined in the same set-up. Kynurenic acid at the higher doses (1-4 microg/min) significantly decreased the thermal hyperalgesia and increased the paw withdrawal latencies on the non-inflamed side. These doses were also associated with motor impairment on both sides. Low doses of kynurenic acid (0.01-0.1 microg/min) potentiated, but did not prolong, the antinociceptive effect of endomorphin-1 (0.1-1 microg/min) on the inflamed side. There was no sign of motor impairment during the combined treatment. These findings demonstrate that the combination of low doses of these two endogenous ligands provides effective and well-controlled antinociception without side effects.
European Journal of Anaesthesiology, 2000
European Journal of Anaesthesiology, 2004
Background and objective: The addition of clonidine to local anaesthetics enhances pain relief af... more Background and objective: The addition of clonidine to local anaesthetics enhances pain relief after peripheral nerve block, but the site of action is unproven. Methods: Seven healthy volunteers underwent three brachial block procedures using bupivacaine 0.25% 1 mg kg Ϫ1 ϩ epinephrine 1 : 200 000 (ϭlocal analgesic) in a randomized, double-blind cross-over fashion: (a) control treatment: local analgesic with 0.9% sodium chloride solution for the block and an intramuscular injection of saline; (b) intramuscular treatment: local analgesic with 0.9% NaCl for block and an intramuscular injection of clonidine 2 µg kg Ϫ1 and (c) block treatment: local analgesic with clonidine 2 µg kg Ϫ1 for block and an intramuscular injection of saline. Results: The onset and duration of complete blockade (sensory/motor/temperature) was evaluated in the four nerve regions of the hand and forearm. Additionally, sedation score, blood pressure, heart rate and plasma clonidine concentrations were determined. The median duration of complete sensory blockade was 270 min (range 0-600) for block treatment compared to 0 min (range 0-480) for intramuscular treatment (P Ͻ 0.05) and 0 min (range 0-180) for control treatment (P Ͻ 0.05). Motor and temperature blockade exhibited similar results. Administration of clonidine was associated with sedation and a decrease in heart rate and blood pressure independent of the route of administration. Plasma clonidine concentrations were lower for block compared to the intramuscular treatment. Conclusions: The admixture of clonidine to bupivacaine plus epinephrine prolongs and enhances brachial plexus blockade. Lower clonidine plasma concentrations for block treatment strongly suggest a local effect.
Chest, 1993
To investigate the frequency and extent of spontaneous changes ("events") in co... more To investigate the frequency and extent of spontaneous changes ("events") in continuously measured mixed venous oxygen saturation (SvO2) in septic patients and to determine whether attention to individual event-frequency offers additional information for patient management. Nonrandomized prospective study. General intensive care unit at a university hospital. Fifteen patients suffering from septic shock and multiple organ dysfunction syndrome. For the continuous assessment of SvO2 a fiberoptic pulmonary artery catheter (Baxter Edwards) was inserted in all patients. A certain event was defined as a sudden change in SvO2 of > or = 5 percent lasting for > 10 min. All events were grouped as either moderate (< or = 10 percent changes in SvO2) or severe events (> 10 percent changes). Hemodynamics and inotropic support, oxygenation and ventilatory support, hemoglobin levels and body temperature were determined at the event and compared with the ultimate values registered before the event. We evaluated 377 events during an observation period of 1,575 h. Patients' mean SvO2 levels ranged between 72 +/- 7 and 82 +/- 4. Desaturations below 65 percent (39 out of 377 events) occurred in 11 patients. Overall, 74 percent of all events were moderate and 26 percent were severe. The incidence of events was 5.6 +/- 1.5 during 24 h in survivors (n = 10) and 6.3 +/- 1.6 during 24 h in nonsurvivors (n = 5). While in survivors only 20 percent of all events were severe events, this portion was significantly higher in nonsurvivors (34 percent; p = 0.03). In 67 percent of all events we observed changes in the registered physiologic parameters or therapeutic interventions probably causing the event. The cause of the remaining 33 percent of all events could not be elucidated. The SvO2 of septic shock patients is mainly normal or even supranormal. However, short-term changes in SvO2 do occur frequently in these patients. Nonsurvivors exhibit a higher frequency as well as a significantly greater severity of events, which may point toward a concealed mismatch of oxygen supply and demand. A high incidence of short-term SvO2 changes in a septic shock patient may be of diagnostic and prognostic significance. Therefore, we recommend the installation of a computerized alarm-function for the automatic detection and indication of frequent events.
Anesthesiology, 1999
Background Intrathecal clonidine produces dose-dependent postoperative analgesia and enhances lab... more Background Intrathecal clonidine produces dose-dependent postoperative analgesia and enhances labor analgesia from intrathecal sufentanil. The authors evaluated the dose-response potency of intrathecally administered clonidine by itself during first stage of labor with respect to analgesia and maternal and fetal side effects. Methods Thirty-six parturients requesting labor analgesia were included in this prospective, randomized, double-blind study. Parturients with < 6 cm cervical dilatation received either 50, 100, or 200 microg intrathecal clonidine. The authors recorded visual analog pain score (VAPS), maternal blood pressure and heart rate, ephedrine requirements, and sedation at regular intervals and fetal heart rate tracings continuously. Duration of analgesia was defined as time from intrathecal clonidine administration until request for additional analgesia. Results Clonidine produced a reduction in VAPS with all three doses. The duration of analgesia was significantly lo...
Anesthesiology, 2000
Background Previous studies suggest that caudal administration of ketamine cause effective analge... more Background Previous studies suggest that caudal administration of ketamine cause effective analgesia. The purpose of the current study was to compare the clinical effectiveness and plasma concentrations of S(+)-ketamine after caudal or intramuscular administration in children to distinguish between local and systemic analgesia. Methods After induction of general anesthesia, 42 patients, aged 1 to 7 yr, scheduled to undergo inguinal hernia repair randomly received a caudal (caudal group) or intramuscular (intramuscular group) injection of 1 mg/kg S(+)-ketamine. Intraoperatively, heart rate (HR), mean arterial pressure (MAP) and arterial oxygen saturation were measured. Postoperative measurements included duration of analgesia, a four-point sedation score, and hemodynamic and respiratory monitoring for 6 h in the recovery room. Analgesic requirements in the recovery room were assessed by an independent blinded observer using an observational pain/discomfort scale (OPS). Plasma samples...
Anesthesiology, 2000
Background The spinal administration of some N-methyl-d-aspartate receptor antagonists results in... more Background The spinal administration of some N-methyl-d-aspartate receptor antagonists results in antinociception and potentiates the effects of opioids and alpha2-adrenoceptor agonists, but ketamine and its enantiomers have not been examined. The present study investigated the interactions of racemic ketamine, R(-)-ketamine and S(+)-ketamine with morphine and with dexmedetomidine. Methods Intrathecal catheters were implanted into male Wistar rats. Three days later, the acute nociceptive sensitivity was assessed using the tail-flick test. Analgesic latencies were converted to the percentage maximum possible effect. The dose that yielded 50% of the maximum possible effect (ED50) and dose-response and time-course curves were determined for the ketamines (30-300 microg), morphine (0.1-3.0 microg), dexmedetomidine (0.3-10.0 microg), and mixtures of two doses of ketamines (30 or 100 microg) with different doses of morphine or dexmedetomidine for fixed-dose analysis. Results Neither racem...
Anesthesiology, 2003
Background Cerebrovascular carbon dioxide reactivity during high-dose remifentanil infusion was i... more Background Cerebrovascular carbon dioxide reactivity during high-dose remifentanil infusion was investigated in volunteers by measurement of regional cerebral blood flow (rCBF) and mean CBF velocity (CBFv). Methods Ten healthy male volunteers with a laryngeal mask for artificial ventilation received remifentanil at an infusion rate of 2 and 4 microg x kg-1 x min-1 under normocapnia, hypocapnia, and hypercapnia. Stable xenon-enhanced computed tomography and transcranial Doppler ultrasonography of the left middle cerebral artery were used to assess rCBF and mean CBFv, respectively. If required, blood pressure was maintained within baseline values with intravenous phenylephrine to avoid confounding effects of altered hemodynamics. Results Hemodynamic parameters were maintained constant over time. Remifentanil infusion at 2 and 4 microg x kg-1 x min-1 significantly decreased rCBF and mean CBFv. Both rCBF and mean CBFv increased as the arterial carbon dioxide tension increased from hypoc...
Anesthesiology, 1999
Background Ropivacaine, a new local anesthetic, is less cardiotoxic in adults and is less likely ... more Background Ropivacaine, a new local anesthetic, is less cardiotoxic in adults and is less likely to cause motor blockade than is bupivacaine. The authors evaluated the clinical effectiveness and hemodynamic effects of ropivacaine compared with bupivacaine and the pharmacokinetics of ropivacaine when given for caudal blocks in 56 children 4.1 +/- 1.2 yr old (mean +/- SD). Methods Patients scheduled for inguinal hernia repair were randomly given a caudal injection (0.75 ml/kg) of ropivacaine, 0.25% (R0.25 group); ropivacaine, 0.5% (R0.5 group); or bupivacaine, 0.25% (B0.25 group). Postoperative measurements included the duration of analgesia, which was our primary outcome variable, and hemodynamic and respiratory monitoring for 4 h in the recovery room. Thereafter, analgesic requirements for the following 24 h were assessed by an independent observer on the ward using an observational pain-discomfort scale, which gives a cumulative score from 5 to 15 to estimate the quality of analges...
Anesthesia & Analgesia, 1998
2.1. Preparation of liposome formulations Structurally multilamellar liposomes were prepared from... more 2.1. Preparation of liposome formulations Structurally multilamellar liposomes were prepared from dipalmitoyl phosphatidyl choline (DPPC)-cholesterol in 50% ratio using the dry-film hydration by vortex mixer Background/aim: Based on our previous in vitro study with multilamellar liposomal bupivacaine (MLB) versus bupivacaine alone in artificial cerebrospinal fluid, we aimed to investigate in vivo antinociceptive effect of intrathecal MLB by determining tail flick latency (TFL) time after thermal stimulation in rats. Materials and methods: After preparing MLB and high-yield drug entrapment in liposome (HYDEL) bupivacaine, 18 female Wistar rats were assigned to 3 groups as control (bupivacaine) and study groups (MLB and HYDEL bupivacaine) including 6 rats in each group to administer these drugs intrathecally. Antinociceptive activity was determined in terms of TFL time after thermal stimulation. Maximum possible effect (MPE) calculated from TFL times and rats with motor block were documented. Results: TFL times after intrathecal injection of HYDEL bupivacaine were significantly longer than that of the control and MLB groups (P < 0.05) and returned to baseline 180 min after intrathecal injection. MPE (100%) with intrathecal HYDEL bupivacaine occurred between 10 to 45 min. Afterwards, MPEs were 70% and 50% for the control and MLB groups, respectively. Motor block disappeared after 20 min in the study groups while it lasted 75 min in the control. Conclusion: Intrathecal administration of MLB and HYDEL bupivacaine in rats resulted in longer duration of antinociceptive activity with shorter motor block duration.
Uploads
Papers by Walter Klimscha