Papers by Jürgen Schüttler
Anesthesiology, 2016
Background Patient-controlled analgesia (PCA) is a common method for postoperative pain therapy, ... more Background Patient-controlled analgesia (PCA) is a common method for postoperative pain therapy, but it is characterized by large variation of plasma concentrations. PCA with target-controlled infusion (TCI-PCA) may be an alternative. In a previous analysis, the authors developed a pharmacokinetic model for hydromorphone. In this secondary analysis, the authors investigated the feasibility and efficacy of TCI-PCA for postoperative pain therapy with hydromorphone. Methods Fifty adult patients undergoing cardiac surgery were enrolled in this study. Postoperatively, hydromorphone was applied intravenously during three sequential periods: (1) as TCI with plasma target concentrations of 1 to 2 ng/ml until extubation; (2) as TCI-PCA with plasma target concentrations between 0.8 and 10 ng/ml during the following 6 to 8 h; and (3) thereafter as PCA with a bolus dose of 0.2 mg until the next morning. During TCI-PCA, pain was regularly assessed using the 11-point numerical rating scale (NRS)....
Journal of Clinical Anesthesia, Mar 1, 2000
Study Objective: To measure the incidence of awareness during induction of anesthesia with etomid... more Study Objective: To measure the incidence of awareness during induction of anesthesia with etomidate and fentanyl, and to model its frequency as a function of dose of etomidate. Design: Prospective cohort study. Setting: Anesthesia department of a university hospital. Patients: 30 ASA physical status I, II, and III patients undergoing elective general surgery. Interventions: Patients were assigned to one of three groups of etomidate (0.2 mg/kg, 0.3 mg/kg, 0.4 mg/kg) and received fentanyl (2 g/kg) and 2 ϫ ED 95 of cisatracurium (0.1 mg/kg). Neuromuscular block was monitored with a peripheral nerve stimulator. Intubation was performed after maximum T 1-depression. To identify awareness, the isolated forearm technique (IFT) was used. The IFT was performed by prompting the patient every 20 seconds. Only a verified response was considered a positive IFT response. Anesthesia was maintained with isoflurane in oxygen/air and fentanyl. Measurements and Main Results: Maximum neuromuscular block occurred after 352 Ϯ 96 seconds and intubation was performed 424 Ϯ 86 seconds after loss of consciousness (LOC). Awareness was dose dependent: 80% of patients receiving 0.2 mg/kg etomidate, 70% of patients receiving 0.3 mg/kg etomidate, and 20% of patients receiving 0.4 mg/kg etomidate had a positive IFT response. Awareness occurred in one patient 3 minutes after LOC, in 65% during laryngoscopy, and in 30% within the following 120 seconds. One patient had explicit recall without finding awareness unpleasant. Hemodynamic parameters did not differ between patients with a positive or a negative IFT response. Conclusions: The incidence of awareness during bolus induction can be modeled as dose
Acta Odontologica Scandinavica, May 27, 2015
Advanced Cardiovascular Life Support (ACLS) in life-threatening situations is perceived as a basi... more Advanced Cardiovascular Life Support (ACLS) in life-threatening situations is perceived as a basic skill for dental professionals. However, medical emergency training in dental schools is often not standardized. The dental students' knowledge transfer to an ACLS setting thus remains questionable. The aim of the study was to evaluate dental pre-doctorate students' practical competence in ACLS in a standardized manner to enable the curriculum to be adapted to meet their particular needs. Thirty dental students (age 25.47 ± 1.81; 16 male/14 female) in their last year of dental studies were randomly assigned to 15 teams. Students' ability to successfully manage ACLS was assessed by a scenario-based approach (training module: Laerdal® ALS Skillmaster). Competence was assessed by means of (a) an observation chart, (b) video analysis and (c) training module analysis (Laerdal HeartSim®4000; Version 1.4). The evaluation was conducted by a trained anesthesiologist with regard to the 2010 guidelines of the European Resuscitation Council (ERC). Only five teams (33.3%) checked for all three vital functions (response, breathing and circulation). All teams initiated cardiopulmonary resuscitation (CPR). Only 54.12% of the compressions performed during CPR were sufficient. Four teams stopped the CPR after initiation. In total, 93% of the teams used the equipment for bag-valve-mask ventilation and 53.3% used the AED (Automated external defibrillator). ACLS training on a regular basis is necessary and, consistent with a close link between dentistry and medicine, should be a standardized part of the medical emergency curriculum for dental students with a specific focus on the deficiencies revealed in this study.
PubMed, 2016
Automated perioperative measurements such as cardiovascular monitoring data are commonly compared... more Automated perioperative measurements such as cardiovascular monitoring data are commonly compared to established upper and lower thresholds, but could also allow for more complex interpretations. Analyzing such time series in extensive electronic medical records for research purposes may itself require customized automation, so we developed a set of algorithms for quantifying different aspects of temporal fluctuations. We implemented conventional measures of dispersion, summaries of absolute gradients between successive values, and Poincaré plots. We aggregated the severity and duration of hypotensive episodes by calculating the average area under different mean arterial pressure (MAP) thresholds. We applied these methods to 30,452 de-identified MAP series, and analyzed the similarity between alternative indices via hierarchical clustering. To explore the potential utility of these propositional metrics, we computed their statistical association with presumed complications due to cardiovascular instability. We observed that hierarchical clustering reliably segregated features that had been designed to quantify dissimilar aspects. Summaries of temporary hypotension turned out to be significantly increased among patient subgroups with subsequent signs of a complicated recovery. These associations were even stronger for measures that were specifically geared to capturing short-term MAP variability. These observations suggest the potential capability of our proposed algorithms for quantifying heterogeneous aspects of short-term MAP fluctuations. Future research might also target a wider selection of outcomes and other attributes that may be subject to intraoperative variability.
Anesthesiology, Sep 1, 1986
BMC Anesthesiology, Oct 2, 2018
Background: The obstructive sleep apnea syndrome (OSAS) is characterized by temporary cerebral hy... more Background: The obstructive sleep apnea syndrome (OSAS) is characterized by temporary cerebral hypoxia which can cause cognitive dysfunction. On the other hand, hypoxia induced neurocognitive deficits are detectable after general anesthesia. The objective of this study was to evaluate the impact of a high risk of OSAS on the postoperative cognitive dysfunction after intravenous anesthesia. Methods: In this single center trial between June 2012 and June 2013 43 patients aged 55 to 80 years with an estimated hospital stay of at least 3 days undergoing surgery were enrolled. Patients were screened for a high risk of OSAS using the STOP-BANG test. The cognitive function was assessed using a neuropsychological test battery, including the DemTect test for cognitive impairment and the RMBT test for memory, the day before surgery and within 36 h after extubation. Results: Twenty-two of the 43 analyzed patients were identified as patients with a high risk of OSAS. Preoperatively, OSAS patients showed a significant worse performance only for the DemTect (p = 0.0043). However, when comparing pre-and postoperative test results, the OSAS patients did not show a significant loss in any test but significantly improved in RMBT test, whereas the control group showed a significant worse performance in three of eight tests. In five tests, we found a significant difference between the two groups with respect to the change from pre-to postoperative cognitive function. Conclusion: Patients with a high risk of OSAS showed a less impairment of memory function and work memory performance after intravenous anesthesia. This might be explained by a beneficial effect of intrinsic hypoxic preconditioning in these patients.
European Journal of Anaesthesiology, Jun 1, 2004
Conclusions: Statistical analysis has shown an initial survival rate of 45% (21% patients died af... more Conclusions: Statistical analysis has shown an initial survival rate of 45% (21% patients died after ICU admission ϩ24% patients survived to ICU discharge). Primary cardiac disease, monitored areas, initial ventricular fibrillation or tachycardia, short time interval from collapse to treatment and short CPR duration can be considered as positive predictive factors of survival to initial resuscitation. References:
Supportive Care in Cancer, Oct 25, 2007
Introduction Studies on opioid use in terminally ill cancer patients have shown a prefinal dose i... more Introduction Studies on opioid use in terminally ill cancer patients have shown a prefinal dose increase in the majority of patients. Mostly oral opioids were used. Due to the pharmacokinetic properties of opioids, it is rather difficult to get a reliable estimate of the true opioid need from those results. Materials and methods Retrospectively, we analyzed opioid use during the last week of life of 30 consecutive outpatients with cancer on intravenous (i.v.) morphine patient-controlled analgesia (PCA). A dose increase (decrease) was defined as an increase (decrease) of the patient's individual daily dose by at least 30% with respect to their prior daily dose. We also analyzed circadian variations in morphine use. Results Thirty patients fulfilled the primary study inclusion criteria. Fulfilling the exclusion criteria, seven patients had to be excluded from analysis (n=3, on PCA for less than 7 days; n=4, PCA was finished before death). Twenty-three patients with a total of 161 treatment days were analyzed. The patients' median age was 57 years (range, 4 to 72). The median duration of intravenous morphine PCA was 19 days (range, 8 to 58). The median daily intravenous morphine dose during the last week of life was 96 to 115 mg, without significant change over time/from day to day (Friedman test). On 144/161 days (89.2%), morphine dose remained stable. On 9 treatment days (5.6%), the dose increased, and on 8 days (5.0%), it decreased. In three patients, only dose increases, and in four patients, only dose decreases were observed. In four patients, both dose increases and decreases were observed. Twelve patients showed no change in daily morphine dose. Opioid use lacked a diurnal pattern. Conclusion During their end-of-life phase, cancer patients on i.v. morphine PCA showed a stable daily opioid need.
Objective-To assess stress hormone response in traumatised patients studied at the site of injury... more Objective-To assess stress hormone response in traumatised patients studied at the site of injury and on their way to hospital. Methods-The study was prospective. Blood samples were taken from 77 patients immediately after the arrival of the emergency physician at the site of the accident (tl) and shortly before patients' admission to hospital (t2). Plasma concentrations of 3 endorphin, cortisol, adrenocorticotrophic hormone (ACTH), prolactin, and growth hormone were measured. Results-Trauma in out-of-hospital patients resulted in remarkably increased concentration of growth hormone within minutes. ACTH, cortisol, and prolactin were only moderately increased. No significant correlations were found between hormone levels and blood pressure or heart rate. The plasma ACTH concentration was significantly lower before admission to hospital than immediately after the accident. Plasma cortisol, prolactin, and growth hormone concentrations were not significantly different between the two points of observation. In samples taken immediately after the accident (tl), there was a positive correlation between both , endorphin and prolactin and the injury severity score, whereas cortisol levels were negatively correlated with injury severity score, suggesting impaired cortisol release from the adrenal cortex after severe injury. At t1 ACTH was correlated with cortisol and (8 endorphin. Patients with head injuries had hormone concentrations similar to those without head injuries but with a similar injury severity score from injuries in other parts of the body. Conclusions-Lower cortisol concentrations in the very severely injured might be due to failure of the adrenal cortex to respond normally to ACTH stimulation. Growth hormone seems to play a major role in the response to trauma, reflecting an immediate stress response.
Anesthesiology, 2007
Background: Milrinone used for acute cardiac insufficiency could be of interest during cardiopulm... more Background: Milrinone used for acute cardiac insufficiency could be of interest during cardiopulmonary resuscitation because of its positive inotropic effects. In this study, the combination of milrinone-vasopressin was compared with epinephrine and vasopressin, as well as with the combination of epinephrine-vasopressin, in reference to hemodynamics. Methods: Thirty-two pigs underwent ligation of the circumflex coronary artery and induction of ventricular fibrillation lasting for 4 min. Cardiopulmonary resuscitation was performed after randomization to one of four groups: epinephrine (30-g/kg bolus), vasopressin (0.4-U/kg bolus), epinephrinevasopressin (15-g/kg epinephrine bolus, 0.2-U/kg vasopressin bolus), or milrinone-vasopressin (0.4-U/kg vasopressin bolus, 50-g/kg milrinone bolus over 5 min and a continuous infusion of 0.4 g ⅐ kg ؊1 ⅐ min ؊1). The hemodynamic variables were measured before cardiopulmonary resuscitation as well as 4, 8, 15, and 30 min after return of spontaneous circulation. Results: All animals were resuscitated successfully. The animals of the milrinone-vasopressin group displayed significantly (P < 0.05) higher cardiac index values (30 min after return of spontaneous circulation: epinephrine, 65.8 ؎ 13.2; vasopressin, 70.7 ؎ 18.3; epinephrine-vasopressin, 69.1 ؎ 36.2; milrinone-vasopressin, 120.7 ؎ 34.8 ml ⅐ min ؊1 ⅐ kg ؊1) without a decrease in mean arterial pressure or coronary perfusion pressure. Conclusions: The combination of vasopressin-milrinone as compared with epinephrine during cardiopulmonary resuscitation leads to an improved cardiac index without relevant decrease of mean arterial pressure or coronary perfusion pressure.
Canadian Journal Of Anesthesia/journal Canadien D'anesthésie, Jun 1, 2001
The present study investigated the interaction between the cumulative dose requirements of cisatr... more The present study investigated the interaction between the cumulative dose requirements of cisatracurium and anesthesia with isoflurane, sevoflurane, desflurane or propofol using closedloop feedback control. Methods: Fifty-six patients (18-85 yr, vitrectomies of more than one hour) were studied. In the volatile anesthetics groups, anesthesia was maintained by 1.3 MAC of isoflurane, sevoflurane or desflurane; in the propofol group, anesthesia was maintained by a continuous infusion of 6-8 mg•kg-1 •hr-1 propofol. After bolus application of 0.1 mg•kg-1 cisatracurium, a T1%-level of 10% of control level (train-of-four stimulation every 20 sec) was maintained using closed-loop feedback controlled infusion of cisatracurium. The effective therapeutic infusion rate (ETI) was estimated from the asymptotic steady-state infusion rate I ss. The I ss was derived from fitting an asymptotic line to the measured cumulative dose requirement curve. The ETI of the different groups was compared using Kruskal-Wallis-test, followed by rank sum test, corrected for the number of comparisons, P <0.05 was regarded as showing significant difference. Results: ETI in the isoflurane group was 35.6 ± 8.6 µg•m-2 •min-1 , in the sevoflurane group 36.4-± 11.9 µg m-2 •min-1 , in the desflurane group 23.8 ± 6.3 µg•m-2 •min-1. The ETI of the volatile anesthetic groups were all significantly lower than the ETI in the propofol group at 61.7 ± 25.3 µg•m-2 •min-1 (P <0.002). The ETI in the desflurane group was significantly lower than in all other groups (P <0.02). Conclusion: In comparison to propofol, isoflurane, sevoflurane and desflurane reduce the cumulative dose requirements of cisatracurium to maintain a 90% neuromuscular blockade by 42%, 41% and 60%, respectively. Objectif : Rechercher l'interaction entre la dose cumulative nécessaire de cisatracurium et l'anesthésie avec de l'isoflurane, du sévoflurane, du desflurane ou du propofol, en utilisant un système de rétroaction en boucle fermée. Résultats : La PTU associée à l'isoflurane a été de 35,6 ± 8,6 mg•m-2 •min-1 ; au sévoflurane, 36,4 ± 11,9 mg m-2 •min-1 et au desflurane, 23,8 ± 6,3 mg•m-2 •min-1. La PTU associée aux anesthésiques volatils a été significativement plus basse que celle qui est associée au propofol, 61,7 ± 25,3 mg•m-2 •min-1 (P <0,002). La PTU associée au desflurane a été significativement plus basse que celles qui concernent tous les autres anesthésiques (P<0,02). Conclusion : Comparés au propofol, l'isoflurane, le sévoflurane et le desflurane réduisent de 42 %, 41 % et 60 %, respectivement, 532 GENERAL ANESTHESIA
European Journal of Anaesthesiology, Jun 1, 2004
thermal hyperalgesia and mechanical allodynia for 7 days. Moreover, remifentanil clearly enhanced... more thermal hyperalgesia and mechanical allodynia for 7 days. Moreover, remifentanil clearly enhanced postoperative pain for 7 days Vs 3 days, in saline operated mice. Conclusion(s): Remifentanil enhanced postoperative pain in mice. Our results corroborate clinical observations showing that relatively large-dose of intraoperative remifentanil increased postoperative pain and morphine consumption in humans (3). Our results provide the first evidence of opioidinduced hyperalgesia in an incisional pain model in mice, presenting a new animal model to study the mechanisms implicated in OIH. References:
Anesthesiology, Sep 1, 2000
Klinische Anästhesiologie und Intensivtherapie, 1994
Erste Versuche, das Elektroenzephalogramm als Instrument zur quantitativen Erfassung der durch An... more Erste Versuche, das Elektroenzephalogramm als Instrument zur quantitativen Erfassung der durch Anasthetika hervorgerufenen Effekte zu benutzen, liegen schon mehr als 50 Jahre zuruck. Eine der ersten Arbeiten zur Abschatzung der „Narkosetiefe“ mit Hilfe des Elektroenzephalogramms war wahrscheinlich die von Gibbs et al. aus dem Jahre 1937 [15]. Spater versuchte die Arbeitsgruppe um Bickford und Faulconer durch eine Klassifizierung der unter Atheranasthesie hervorgerufenen morphologischen EEG-Veranderungen eine elektrophysiologische Stadieneinteilung der „Narkosetiefe“ zu definieren [11, 25]. Die „Narkosetiefe“ wurde in 6 Stadien eingeteilt, wobei die Zuordnung zu den einzelnen Stadien masgeblich von den beobachteten morphologischen Anderungen im EEG-Muster abhangig war. Diese Einteilung konnte man schon als fruhen Versuch der Weiterentwicklung des Guedel-Schemas [16] auf elektrophysiologischer Basis verstehen.
EBioMedicine, 2018
Background: Small fiber neuropathy (SFN) is a severe and disabling chronic pain syndrome with no ... more Background: Small fiber neuropathy (SFN) is a severe and disabling chronic pain syndrome with no causal and limited symptomatic treatment options. Mechanistically based individual treatment is not available. We report an in-vitro predicted individualized treatment success in one therapy-refractory Caucasian patient suffering from SFN for over ten years. Methods: Intrinsic excitability of human induced pluripotent stem cell (iPSC) derived nociceptors from this patient and respective controls were recorded on multi-electrode (MEA) arrays, in the presence and absence of lacosamide. The patient's pain ratings were assessed by a visual analogue scale (10: worst pain, 0: no pain) and treatment effect was objectified by microneurography recordings of the patient's single nerve C-fibers. Findings: We identified patient-specific changes in iPSC-derived nociceptor excitability in MEA recordings, which were reverted by the FDA-approved compound lacosamide in vitro. Using this drug for individualized treatment of this patient, the patient's pain ratings decreased from 7.5 to 1.5. Consistent with the pain relief reported by the patient, microneurography recordings of the patient's single nerve fibers mirrored a reduced spontaneous nociceptor (C-fiber) activity in the patient during lacosamide treatment. Microneurography recordings yielded an objective measurement of altered peripheral nociceptor activity following treatment. Interpretation: Thus, we are here presenting one example of successful patient specific precision medicine using iPSC technology and individualized therapeutic treatment based on patient-derived sensory neurons.
Journal of Critical Care, 2018
To investigate long-term effects of staff training and electronic clinical decision support (CDS)... more To investigate long-term effects of staff training and electronic clinical decision support (CDS) on adherence to lung-protective ventilation recommendations. Materials and methods: In 2012, group instructions and workshops at two surgical intensive care units (ICUs) started, focusing on standardized protocols for mechanical ventilation and volutrauma prevention. Subsequently implemented CDS functions continuously monitor ventilation parameters, and from 2015 triggered graphical notifications when tidal volume (V T) violated individual thresholds. To estimate the effects of these educational and technical interventions, we retrospectively analyzed nine years of V T records from routine care. As outcome measures, we calculated relative frequencies of settings that conform to recommendations, case-specific mean excess V T , and total ICU survival. Results: Assessing 571,478 V T records from 10,241 ICU cases indicated that adherence during pressure-controlled ventilation improved significantly after both interventions; the share of conforming V T records increased from 61.6% to 83.0% and then 86.0%. Despite increasing case severity, ICU survival remained nearly constant over time. Conclusions: Staff training effectively improves adherence to lung-protective ventilation strategies. The observed CDS effect seemed less pronounced, although it can easily be adapted to new recommendations. Both interventions, which futures studies could deploy in combination, promise to improve the precision of mechanical ventilation.
European journal of drug metabolism and pharmacokinetics, Jan 21, 2016
We recently developed a new population pharmacokinetic model for hydromorphone in patients includ... more We recently developed a new population pharmacokinetic model for hydromorphone in patients including age and bodyweight as covariates. The aim of the present study was to evaluate prospectively the predictive performance of this new model during postoperative pain therapy. This was a prospective, single-blinded, randomized, single-center study with two parallel arms. Fifty patients aged 40-85 years undergoing cardiac surgery involving thoracotomy were enrolled. Hydromorphone was administered postoperatively on the intensive care unit as target controlled infusion (TCI) for patient controlled analgesia (TCI-PCA) using the new pharmacokinetic model, or as conventional patient controlled analgesia (PCA). Arterial blood samples were taken for measurement of the hydromorphone plasma concentration. The predictive performance of the pharmacokinetic model was assessed by the median performance error (MDPE), the median absolute performance error (MDAPE), wobble and divergence. For comparison...
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Papers by Jürgen Schüttler