Andreas Duma

Nitrous Oxide for Treatment-Resistant Major Depression: A Proof-of-Concept Trial

BACKGROUND N-methyl-D-aspartate receptor antagonists, such as ketamine, have rapid antidepressant effects in patients with treatment-resistant depression (TRD). We hypothesized that nitrous oxide, an inhalational general anesthetic and N-methyl-D-aspartate receptor antagonist, may also be a rapidly acting treatment for TRD. METHODS In this blinded, placebo-controlled crossover trial, 20 patients with TRD were randomly assigned to 1-hour inhalation of 50% nitrous oxide/50% oxygen or 50% nitrogen/50% oxygen (placebo control). The primary endpoint was the change on the 21-item Hamilton Depression Rating Scale (HDRS-21) 24 hours after treatment. RESULTS Mean duration of nitrous oxide treatment was 55.6 ± 2.5 (SD) min at a median inspiratory concentration of 44% (interquartile range, 37%-45%). In two patients, nitrous oxide treatment was briefly interrupted, and the treatment was discontinued in three patients. Depressive symptoms improved significantly at 2 hours and 24 hours after receiving nitrous oxide compared with placebo (mean HDRS-21 difference at 2 hours, -4.8 points, 95% confidence interval [CI], -1.8 to -7.8 points, p = .002; at 24 hours, -5.5 points, 95% CI, -2.5 to -8.5 points, p < .001; comparison between nitrous oxide and placebo, p < .001). Four patients (20%) had treatment response (reduction ≥50% on HDRS-21) and three patients (15%) had a full remission (HDRS-21 ≤ 7 points) after nitrous oxide compared with one patient (5%) and none after placebo (odds ratio for response, 4.0, 95% CI, .45-35.79; OR for remission, 3.0, 95% CI, .31-28.8). No serious adverse events occurred; all adverse events were brief and of mild to moderate severity. CONCLUSIONS This proof-of-concept trial demonstrated that nitrous oxide has rapid and marked antidepressant effects in patients with TRD.

Over-the-head cardiopulmonary resuscitation improves efficacy in basic life support performed by professional medical personnel with a single rescuer: a simulation study.

Two-rescuer cardiopulmonary resuscitation (CPR) is considered the best method for professional basic life support (BLS). However, in many prehospital cardiac arrest situations, one rescuer has to begin CPR alone while the other performs additional tasks. In theory, over-the-head CPR is a suitable alternative in this situation, with the added benefit of allowing the single rescuer to use a self-inflating bag for ventilation. In this trial, we compared standard single-rescuer CPR with over-the-head CPR in manikins. We planned this study using a crossover study design where each participant administered both CPR techniques in a randomized order. Ventilation and chest compression data were collected with analysis software during a 2-min CPR test for each technique. Sixty-seven emergency medical technician students participated in this trial. Over-the-head CPR allowed for superior ventilation compared to standard CPR (number of correct ventilations: 330 of 760 versus 279 of 779; P = 0.002). The quality of delivered chest compressions did not differ between the two groups (correct chest compressions: 4293 of 6304 versus 4313 of 6395; P = 0.44). In conclusion, our study has shown that over-the-head CPR may be an effective alternative BLS technique when a single professional rescuer has to perform CPR, likely offering superior ventilation and comparable chest compression quality compared with standard BLS.

Tube-in-tube Emergency Airway Management after a Bitten Endotracheal Tube Caused by Repetitive Transcranial Electrical Stimulation during Spinal Cord Surgery

WE report a case of bite damage to a wire-reinforced endotracheal tube caused by transcranial electrical stimulation (TES). A 23-yr-old female patient (American Society of Anesthesiologists grade I) with mild motor deficits in the lower extremities was admitted for the extirpation of an intramedullary cervical spinal cord tumor (C3–C7). Intraoperative neurophysiological monitoring by using motor-evoked potentials (MEPs) elicited by TES and somatosensory-evoked potentials was performed to assess the functional integrity of the spinal cord. After induction of general anesthesia by using bolus administration of propofol, remifentanil, and muscle relaxation (0.6 mg/kg rocuronium), a 7.5-mm ID armoured endotracheal tube with cuff (Rüschflex; Teleflex, Kernen, Germany) was introduced, cuffed, and fixed with adhesive tape. A gauze bite block was placed in the recommended manner to prevent bite injuries because tongue bites, lip lacerations, and even a unique case of mandibular fracture were reported during TES in patients without bite block. Anesthesia was maintained by continuous infusion of propofol (100 g · kg 1 · min ) and remifentanil (0.5 g · kg 1 · min ). The neuromuscular blockade was omitted after induction of general anesthesia to avoid interference with MEP monitoring. Neurosurgical access was intended from the posterior; therefore, the patient was turned to a prone position, and TES for MEP monitoring was initiated. Scalp electrodes at positions C3 and C4 were used for TES according to the International 10–20 electroencephalography electrode system. Short trains of 5–7 electrical pulses (frequency 250 Hz, duration of each stimulus 0.5 ms, intensity 80 to 250 V) were applied via corkscrew electrodes originating from a Nicolet Endeavor (Viasys Healthcare, Madison, WI) constant current stimulator to monitor MEPs from limb muscles. Single stimuli of TES were used to record epidural MEPs from an intraoperatively placed epidural catheter electrode. At critical stages of the surgical procedure, short trains of stimuli were used at a rate of 1.1 Hz to continuously assess the functional integrity of motor tracts. During the entire surgical procedure, a total of 4,200 trains of stimuli were applied. Approximately 6 h after incision, the ventilator alarmed leakage. At this point, oxygenation and ventilation could only be performed by high-flow hand ventilation with 100% oxygen. Direct inspection of the endotracheal tube with the patient remaining in prone position revealed a bitten hole near the incisors (fig. 1), although the gauze bite block was still correctly in place. In this emergency situation, a thinner, 5 mm endotracheal tube (Microcuff; Kimberly-Clark, Neenah, WI) (table 1) was inserted into the injured endotracheal tube

Improving Prediction of Postoperative Myocardial Infarction With High-Sensitivity Cardiac Troponin T and NT-proBNP.

BACKGROUND: This study sought to determine whether preoperatively measured high-sensitivity cardiac troponin T (hs-cTnT) and N-terminal pro-brain natriuretic peptide (NT-proBNP) improve cardiac risk prediction in patients undergoing major noncardiac surgery compared with the standard risk indices. METHODS: In this ancillary study to the Vitamins in Nitrous Oxide trial, patients were included who had preoperative hs-cTnT and NT-proBNP measured (n = 572). Study outcome was the incidence of postoperative myocardial infarction (MI) within the first 3 postoperative days. hs-cTnT was considered elevated if >14 ng/L and NT-proBNP if >300 ng/L. Additional cutoff values were investigated on the basis of receiver operating characteristic statistics. Biomarker risk prediction was compared with Lee’s Revised Cardiac Risk Index (RCRI) with the use of standard methods and net reclassification index. RESULTS: The addition of hs-cTnT (>14 ng/L) and NT-proBNP (>300 ng/L) to RCRI significantly improved the prediction of postoperative MI (event rate 30/572 [5.2%], Area under the receiver operating characteristic curve increased from 0.590 to 0.716 with a 0.66 net reclassification index [95% confidence interval 0.32–0.99], P < .001). The use of 108 ng/L as a cutoff for NT-proBNP improved sensitivity compared with 300 ng/L (0.87 vs 0.53). Sensitivity, specificity, positive, and negative predictive value for hs-cTnT were 0.70, 0.60, 0.09, and 0.97 and for NT-proBNP were 0.53, 0.68, 0.08, and 0.96. CONCLUSIONS: The addition of cardiac biomarkers hs-cTnT and NT-proBNP to RCRI improves the prediction of adverse cardiac events in the immediate postoperative period after major noncardiac surgery. The high negative predictive value of preoperative hs-cTnT and NT-proBNP suggest usefulness as a “rule-out” test to confirm low risk of postoperative MI.

High-sensitivity Cardiac Troponin Elevation after Electroconvulsive Therapy: A Prospective, Observational Cohort Study

Background: While electroconvulsive therapy is widely regarded as a lifesaving and safe procedure, evidence regarding its effects on myocardial cell injury is sparse. The objective of this investigation was to determine the incidence and magnitude of new cardiac troponin elevation after electroconvulsive therapy using a novel high-sensitivity cardiac troponin I assay. Methods: This was a prospective cohort study in adult patients undergoing electroconvulsive therapy in a single academic center (up to three electroconvulsive therapy treatments per patient). The primary outcome was new high-sensitivity cardiac troponin I elevation after electroconvulsive therapy, defined as an increase of high-sensitivity cardiac troponin I greater than 100% after electroconvulsive therapy compared to baseline with at least one value above the limit of quantification (10 ng/l). Twelve-lead electrocardiogram and high-sensitivity cardiac troponin I values were obtained before and 15 to 30 min after electroconvulsive therapy; in a subset of patients, an additional 2-h high-sensitivity cardiac troponin I value was obtained. Results: The final study population was 100 patients and a total of 245 electroconvulsive therapy treatment sessions. Eight patients (8 of 100; 8%) experienced new high-sensitivity cardiac troponin I elevation after electroconvulsive therapy with a cumulative incidence of 3.7% (9 of 245 treatments; one patient had two high-sensitivity cardiac troponin I elevations), two of whom had a non–ST-elevation myocardial infarction (incidence 2 of 245; 0.8%). Median high-sensitivity cardiac troponin I concentrations did not increase significantly after electroconvulsive therapy. Tachycardia and/or elevated systolic blood pressure developed after approximately two thirds of electroconvulsive therapy treatments. Conclusions: Electroconvulsive therapy appears safe from a cardiac standpoint in a large majority of patients. A small subset of patients with preexisting cardiovascular risk factors, however, may develop new cardiac troponin elevation after electroconvulsive therapy, the clinical relevance of which is unclear in the absence of signs of myocardial ischemia.

The hematological effects of nitrous oxide anesthesia in pediatric patients.

BACKGROUND:Prolonged administration of nitrous oxide causes an increase in plasma homocysteine in children via vitamin B12 inactivation. However, it is unclear whether nitrous oxide doses used in clinical practice cause adverse hematological effects in pediatric patients. METHODS:This retrospective study included 54 pediatric patients undergoing elective spinal surgery: 41 received nitrous oxide throughout anesthesia (maintenance group), 9 received nitrous oxide for induction and/or emergence (induction/emergence group), and 4 did not receive nitrous oxide (nitrous oxide–free group). Complete blood counts obtained before and up to 4 days after surgery were assessed for anemia, macrocytosis/microcytosis, anisocytosis, hyperchromatosis/hypochromatosis, thrombocytopenia, and leukopenia. The change (&Dgr;) from preoperative to the highest postoperative value was calculated for mean corpuscular volume (MCV) and red cell distribution width (RDW). RESULTS:No pancytopenia was present in any patient after surgery. All patients had postoperative anemia, and none had macrocytosis. Postoperative MCV (mean [99% confidence interval]) peaked at 86 fL (85–88 fL), 85 fL (81–89 fL), and 88 fL (80–96 fL) and postoperative RDW at 13.2% (12.8–13.5%), 13.3% (12.7–13.8%), and 13.0% (11.4–14.6%) for the maintenance group, the induction/emergence group, and the nitrous oxide–free group. Two patients in the maintenance group (5%) developed anisocytosis (RDW >14.6%), but none in the induction/emergence group or in the nitrous oxide–free group (P = 0.43). Both &Dgr;MCV (P = 0.52) and &Dgr;RDW (P = 0.16) were similar across all groups. CONCLUSIONS:Nitrous oxide exposure for up to 8 hours is not associated with megaloblastic anemia in pediatric patients undergoing major spinal surgery.

High-Fidelity Analysis of Perioperative QTc Prolongation.

BACKGROUND:Prolongation of the QTc interval indicates abnormal cardiac repolarization. A recent study has shown that postoperative QTc prolongation is common. However, it is unknown whether QTc prolongation is an isolated postoperative phenomenon or occurs regularly during surgery, or whether the type of anesthesia influences its incidence. METHODS:To answer this question, we conducted a prospective cohort study (n = 300), where QTc duration was continuously recorded by 12-lead Holter electrocardiogram from 30 minutes preoperatively to up to 60 minutes postoperatively. QTc prolongation was compared between adult patients with at least 1 cardiac risk factor undergoing general (n = 101) or spinal anesthesia (n = 99) for orthopedic surgery, or local anesthesia (n = 100). Primary outcome was intraoperative QTc increase (&Dgr;QTc, as defined by the intraoperative-to-preoperative QTc duration difference). The incidence of long QTc episodes (QTc > 500 milliseconds for at least 15 minutes) was also determined. RESULTS:Significant QTc prolongation (median; interquartile range [IQR]) occurred during general anesthesia (&Dgr;QTc, +33 milliseconds; IQR, +22 to 46 milliseconds) and spinal anesthesia (&Dgr;QTc, +22 milliseconds; IQR, +12 to 29 milliseconds), whereas no QTc prolongation was observed during local anesthesia (biopsy, n = 53: &Dgr;QTc, +4 milliseconds; IQR, −4 to +7 milliseconds; coronary angiography, n = 47: &Dgr;QTc, +6 milliseconds; IQR, −5 to +16 milliseconds). The incidence of long QTc episodes was significantly different between general anesthesia (n = 6/63, 9.5%), spinal anesthesia (n = 1/56, 1.8%), local anesthesia for biopsy (n = 0/46, 0%), and coronary angiography (n = 0/19, 0%; P = 0.045). CONCLUSIONS:These results indicate that QTc prolongation is not an isolated postoperative phenomenon and is common during surgery under general and spinal anesthesia.

The effect of nitrous oxide anesthesia on early postoperative opioid consumption and pain.

Background and Objectives Many patients experience moderate to severe postoperative pain. Nitrous oxide (N2O) exerts analgesia by inhibition of N-methyl-D-aspartate receptors. Ketamine, another N-methyl-D-aspartate receptor antagonist, reduces postoperative opioid consumption and pain. A similar effect of N2O is plausible, yet understudied. The goal of this study was to determine the effects of N2O anesthesia on early postsurgical opioid consumption and pain. Methods This was a retrospective, secondary analysis of the Vitamins In Nitrous Oxide trial, where 500 patients undergoing general anesthesia for noncardiac surgery received 60% N2O and 125 received no N2O (otherwise, inclusion/exclusion criteria were identical). Exclusion criteria for this study were regional anesthesia, not extubated after surgery, transfer to intensive care unit, no available postanesthesia care unit record, postsurgical sedation, or treated with naloxone. Primary outcomes were cumulative opioid consumption measured in morphine equivalents and pain scores during the immediate recovery phase. Results Four hundred forty-two patients met inclusion criteria. No difference in intraoperative and postoperative opioid consumption was observed between patients who received N2O (n = 353) and patients who did not (n = 89). The median [interquartile range] postoperative morphine equivalent dose was 6.7 mg [1.7–14.1 mg] for patients who received N2O and 6.7 mg [2.1–15.4 mg] for patients who did not (P = 0.73). The maximum pain score was 6 [4–8] for patients who received N2O versus 6 [3–8] for patients who received N2O-free anesthesia (P = 0.52). The prevalence of moderate to severe pain was 69% for patients who received N2O and 68% for patients who did not (P = 0.90). Conclusions Nitrous oxide anesthesia was not associated with decreased opioid administration, pain, or incidence of moderate to severe pain in the early postoperative phase.

Use of ropivacain and lidocaine for axillary plexus blockade

OBJECTIVE The use of certain peripheral nerve blocks in paediatric patients is gaining increasing popularity, although distinctive characteristics of the juvenile anatomy, psychological barriers, time constraints on block placement, and risks of neurotoxic and cardio toxic side effects are still mentioned. However, newer agents like Ropivacaine and Levobupivacaine seem to offer excellent alternatives to Bupivacaine and Lidocaine, especially for use in paediatric patients. MATERIALS AND METHODS We evaluated Ropivacaine 0.5% and Lidocaine 1.0% using axillary plexus blockade as a single-shot technique in 50 children in the age group of 2 to 10 years and undergoing short upper limb surgery. The primary objectives were to compare onset time, duration and quality of block and the incidence of breakthrough pain. RESULTS Onset time was longer in the Ropivacaine group (15.4 minutes) than in the Lidocaine group (8.2 minutes). The duration of the effect was greater in patients in the Ropivacaine group (337 minutes) than in the Lidocaine group (137 minutes). Duration appeared to vary with patients age but this effect was not statistically significant. CONCLUSION Axillary plexus anaesthesia provides satisfactory perioperative pain relief in infants undergoing short-trauma surgery. Apart from its safety, these results underline that Ropivacaine 0.5% can be recommended for axillary brachial plexus block in children.

Pharmacokinetics and Bioavailability of Inhaled Esketamine in Healthy Volunteers.

Background: Esketamine is traditionally administered via intravenous or intramuscular routes. In this study we developed a pharmacokinetic model of inhalation of nebulized esketamine with special emphasis on pulmonary absorption and bioavailability. Methods: Three increasing doses of inhaled esketamine (dose escalation from 25 to 100 mg) were applied followed by a single intravenous dose (20 mg) in 19 healthy volunteers using a nebulizer system and arterial concentrations of esketamine and esnorketamine were obtained. A multicompartmental pharmacokinetic model was developed using population nonlinear mixed-effects analyses. Results: The pharmacokinetic model consisted of three esketamine, two esnorketamine disposition and three metabolism compartments. The inhalation data were best described by adding two absorption pathways, an immediate and a slower pathway, with rate constant 0.05 ± 0.01 min–1 (median ± SE of the estimate). The amount of esketamine inhaled was reduced due to dose-independent and dose-dependent reduced bioavailability. The former was 70% ± 5%, and the latter was described by a sigmoid EMAX model characterized by the plasma concentration at which absorption was impaired by 50% (406 ± 46 ng/ml). Over the concentration range tested, up to 50% of inhaled esketamine is lost due to the reduced dose-independent and dose-dependent bioavailability. Conclusions: We successfully modeled the inhalation of nebulized esketamine in healthy volunteers. Nebulized esketamine is inhaled with a substantial reduction in bioavailability. Although the reduction in dose-independent bioavailability is best explained by retention of drug and particle exhalation, the reduction in dose-dependent bioavailability is probably due to sedation-related loss of drug into the air.