Dexamethasone for the treatment of established postoperative nausea and vomiting: A randomised dose finding trial.

BACKGROUND: Dexamethasone is widely used for the prevention of postoperative nausea and vomiting (PONV) but little is known about its efficacy for the treatment of established PONV. OBJECTIVE: To test the antiemetic efficacy of intravenous dexamethasone for the treatment of established PONV in adults undergoing surgery under general anaesthesia and to determine whether there is dose-responsiveness. DESIGN: The DexPonv trial is a multicentre, placebo-controlled, randomised, double-blind, dose-finding study. Inclusion of patients was between September 2012 and November 2017. Follow-up for PONV symptoms was for 24 h. Thirty days postoperatively, patients were contacted by study nurses for any information on postoperative bleeding and infection. SETTING: Four public hospitals in Switzerland. PATIENTS: A total of 803 adults scheduled for elective surgery without any antiemetic prophylaxis signed the consent form; 714 were included. Among those, 319 had PONV and 281 patients were eventually randomised (intention to treat population and safety set). The per protocol set consisted of 260 patients. INTERVENTIONS: Patients with PONV symptoms (including retching) were randomised to a single intravenous dose of dexamethasone 3, 6 or 12 mg or matching placebo. MAIN OUTCOME MEASURES: The primary endpoint was the absence of further nausea or vomiting (including retching), within 24 h after administration of the study drug. RESULTS: Dexamethasone was ineffective during the first 24 h, whatever the dosage, compared to placebo, even when the model was adjusted for known risk factors (P = 0.170). There were no differences in the time to treatment failure or the quality of sleep during the first night. There was a positive correlation between the dose of dexamethasone and blood glucose concentrations (P < 0.001), but not with bleeding risk, wound infections or other adverse effects. CONCLUSION: This randomised trial failed to show anti-emetic efficacy of any of the tested intravenous regimens of dexamethasone for the treatment of established PONV in adults undergoing surgery under general anaesthesia. TRIAL REGISTRATION: clinicaltrials.gov (NCT01975727).

Rapid Sequence Induction With a Standard Intubation Dose of Rocuronium After Magnesium Pretreatment Compared With Succinylcholine: A Randomized Clinical Trial.

BACKGROUND: Succinylcholine remains the muscle relaxant of choice for rapid sequence induction (RSI) but has many adverse effects. High-dose rocuronium bromide may be an alternative to succinylcholine for RSI but recovery times are nearly doubled compared with a standard intubating dose of rocuronium. Magnesium sulfate significantly shortens the onset time of a standard intubating dose of rocuronium. We set out to investigate whether intravenous (IV) pretreatment with MgSO4 followed by a standard intubating dose of rocuronium achieved superior intubation conditions compared with succinylcholine. METHODS: Adults were randomized to receive a 15-minute IV infusion of MgSO4 (60 mg·kg-1) immediately before RSI with propofol 2 mg·kg-1, sufentanil 0.2 µg·kg-1 and rocuronium 0.6 mg·kg-1, or a matching 15-minute IV infusion of saline immediately before an identical RSI, but with succinylcholine 1 mg·kg-1. Primary end point was the rate of excellent intubating conditions 60 seconds after administration of the neuromuscular blocking agent and compared between groups using multivariable log-binomial regression model. Secondary end points were blood pressure and heart rate before induction, before and after intubation, and adverse events up to 24 hours postoperatively. RESULTS: Among 280 randomized patients, intubating conditions could be analyzed in 259 (133 MgSO4-rocuronium and 126 saline-succinylcholine). The rate of excellent intubating conditions was 46% with MgSO4-rocuronium and 45% with saline-succinylcholine. The analysis adjusted for gender and center showed no superiority of MgSO4-rocuronium compared with saline-succinylcholine (relative risk [RR] 1.06, 95% confidence interval [CI], 0.81-1.39, P = .659). The rate of excellent intubating conditions was higher in women (54% [70 of 130]) compared with men (37% [48 of 129]; adjusted RR 1.42, 95% CI, 1.07-1.91, P = .017). No significant difference between groups was observed for systolic and diastolic blood pressures. Mean heart rate was significantly higher in the MgSO4-rocuronium group. The percentage of patients with at least 1 adverse event was lower with MgSO4-rocuronium (11%) compared with saline-succinylcholine (28%) (RR 0.38, 95% CI, 0.22-0.66, P < .001). With saline-succinylcholine, adverse events consisted mainly of postoperative muscle pain (n = 26 [19%]) and signs of histamine release (n = 13 [9%]). With MgSO4-rocuronium, few patients had pain on injection, nausea and vomiting, or skin rash during the MgSO4-infusion (n = 5 [4%]). CONCLUSIONS: IV pretreatment with MgSO4 followed by a standard intubating dose of rocuronium did not provide superior intubation conditions to succinylcholine but had fewer adverse effects.

Assessment of spontaneous neuromuscular recovery: A comparison of the TOF-Cuff® with the TOF Watch SX®.

BACKGROUND: TOF-Cuff® is a modified blood pressure cuff used to monitor neuromuscular block. We compared the assessment of spontaneous neuromuscular recovery between TOF-Cuff® (test device) and TOF Watch SX® (reference device). METHODS: Forty patients aged 18-65 years undergoing elective surgery were enrolled. TOF-Cuff® was installed on an upper arm and the TOF Watch SX® on the thumb of the opposite side. Anaesthesia was induced and maintained with intravenous propofol and sufentanil. After induction, the devices were calibrated and continuous train-of-four (TOF) stimulation was started. A single intravenous dose of rocuronium (0.6 mg kg-1 ) was administered for intubation. The primary outcome was total recovery time (time in minutes from the injection of rocuronium to a normalized TOF ratio of 90%). Agreement between the two devices was calculated using mean difference and limits of agreement. RESULTS: The primary outcome could be analysed in 27 patients because of 13 exclusions due to neuromuscular block reversal for shorter procedure surgical time, necessity of reinjection of rocuronium or technical failures of one of the two devices. Median total recovery time with the test device was 45 minutes (interquartile range [IQR] 38.5-61.5) and 63 minutes (IQR 51.1-74.5) with the reference device. Total recovery time with the test device was on average 16.4 minutes shorter (limits of agreement, -6.1 to 39); increasing total recovery time was associated with increasing difference. The TOF ratio of the reference device was on average 0.59 (SD 0.23) when the test device indicated complete recovery. The TOF ratio of the test device was on average 0.98 (SD 0.03) when the reference device indicated complete recovery. CONCLUSION: When compared with the TOF Watch SX® , TOF-Cuff® overestimates spontaneous recovery of a rocuronium-induced neuromuscular block.

The optimal dose of succinylcholine for rapid sequence induction: a systematic review and meta-analysis of randomized trials.

BACKGROUND: The evidence base for the widely accepted standard regimen of succinylcholine for rapid sequence induction (1.0 mg kg- 1) remains unclear. METHODS: We performed a systematic review and meta-analysis of randomized trials comparing any succinylcholine regimen with the standard regimen (1.0 mg kg- 1) and reporting on intubating conditions and/or apnoea times. Results were expressed as absolute risk differences (ARD) for dichotomous data and mean differences (MD) for continuous data. RESULTS: We retrieved six trials with relevant data of 864 patients (ASA 1 or 2, aged 18-65 years, body mass index < 30 kg m- 2). Four regimens (0.3, 0.4, 0.5, 0.6 mg kg- 1) were compared with 1.0 mg kg- 1 in at least three trials each, and three (0.8, 1.5, 2 mg kg- 1) in one each. With 0.3 to 0.5 mg kg- 1, the likelihood of excellent intubating conditions was significantly decreased (ARD - 22% to - 67%). With 0.3 and 0.4 mg kg- 1, but not with 0.5, 0.6, 0.8, 1.5 and 2.0 mg kg- 1, the likelihood of unacceptable intubating conditions was significantly increased (ARD + 22% and + 32%, respectively). With 2.0 mg kg- 1, but not with 0.8 or 1.5 mg kg- 1, the likelihood of excellent intubating conditions was significantly increased (ARD + 23%). Apnoea times were significantly shorter with regimens ≤0.8 mg kg- 1 (MD - 1.0 to - 3.4 min) but were not reported with 1.5 or 2.0 mg kg- 1. CONCLUSIONS: With succinylcholine regimens ≤0.5 mg kg- 1, excellent intubating conditions are less likely and apnoea times are shorter, compared with 1 mg kg- 1. With 0.3 and 0.4 mg kg- 1, unacceptable intubating conditions are more common. Succinylcholine 1.5 mg kg- 1 does not produce more often excellent conditions compared with 1 mg kg- 1, while 2.0 mg kg- 1 does, but the database with these regimens is weak and apnoea times remain unknown. Limited information size and strong statistical heterogeneity decrease the certainty of the evidence.

Reclassifying Anaphylaxis to Neuromuscular Blocking Agents Based on the Presumed Patho-Mechanism: IgE-Mediated, Pharmacological Adverse Reaction or "Innate Hypersensitivity"?

Approximately 60% of perioperative anaphylactic reactions are thought to be immunoglobulin IgE mediated, whereas 40% are thought to be non-IgE mediated hypersensitivity reactions (both considered non-dose-related type B adverse drug reactions). In both cases, symptoms are elicited by mast cell degranulation. Also, pharmacological reactions to drugs (type A, dose-related) may sometimes mimic symptoms triggered by mast cell degranulation. In case of hypotension, bronchospasm, or urticarial rash due to mast cell degranulation, identification of the responsible mechanism is complicated. However, determination of the type of the underlying adverse drug reaction is of paramount interest for the decision of whether the culprit drug may be re-administered. Neuromuscular blocking agents (NMBA) are among the most frequent cause of perioperative anaphylaxis. Recently, it has been shown that NMBA may activate mast cells independently from IgE antibodies via the human Mas-related G-protein-coupled receptor member X2 (MRGPRX2). In light of this new insight into the patho-mechanism of pseudo-allergic adverse drug reactions, in which as drug-receptor interaction results in anaphylaxis like symptoms, we critically reviewed the literature on NMBA-induced perioperative anaphylaxis. We challenge the dogma that NMBA mainly cause IgE-mediated anaphylaxis via an IgE-mediated mechanism, which is based on studies that consider positive skin test to be specific for IgE-mediated hypersensitivity. Finally, we discuss the question whether MRGPRX2 mediated pseudo-allergic reactions should be re-classified as type A adverse reactions.

Non-IgE-Dependent Hypersensitivity to Rocuronium Reversed by Sugammadex: Report of Three Cases and Hypothesis on the Underlying Mechanism.

We present 3 cases of pseudoallergic (anaphylactoid) reactions to perioperatively administered rocuronium, which rapidly resolved after sugammadex injection. Allergological workup showed no evidence for immediate-type hypersensitivity to the drugs used for anesthesia, including rocuronium. However, rocuronium induced an irritative reaction in skin tests in all 3 patients and in 3 healthy individuals. This reaction was specifically suppressed by adding sugammadex at a 1:1 molecular proportion to rocuronium before the skin tests. This observation suggests that the patients suffered from a pseudoallergic reaction, and indicates that sugammadex might act via the inhibition of non-IgE mediated MRGPRX2 (Mas-related G-protein-coupled receptor member X2)-triggered mast cell degranulation induced by rocuronium.

Efficacy of sugammadex for the reversal of moderate and deep rocuronium-induced neuromuscular block in patients pretreated with intravenous magnesium: a randomized controlled trial.

BACKGROUND: Magnesium enhances the effect of rocuronium. Sugammadex reverses rocuronium-induced neuromuscular block. The authors investigated whether magnesium decreased the efficacy of sugammadex for the reversal of rocuronium-induced neuromuscular block. METHODS: Thirty-two male patients were randomized in a double-blinded manner to receive magnesium sulfate (MgSO4) 60 mg/kg or placebo intravenously before induction of anesthesia with propofol, sufentanil, and rocuronium 0.6 mg/kg. Neuromuscular transmission was monitored using TOF-Watch SX acceleromyography (Organon Ltd., Dublin, Ireland). In 16 patients, sugammadex 2 mg/kg was administered intravenously at reappearance of the second twitch of the train-of-four (moderate block). In 16 further patients, sugammadex 4 mg/kg was administered intravenously at posttetanic count 1 to 2 (deep block). Primary endpoint was recovery time from injection of sugammadex to normalized train-of-four ratio 0.9. Secondary endpoint was recovery time to final T1. RESULTS: Average time for reversal of moderate block was 1.69 min (SD, 0.81) in patients pretreated with MgSO4 and 1.76 min (1.13) in those pretreated with placebo (P = 0.897). Average time for reversal of deep block was 1.77 min (0.83) in patients pretreated with MgSO4 and 1.98 min (0.58) in those pretreated with placebo (P = 0.572). Times to final T1 were longer compared with times to normalized train-of-four ratio 0.9, without any difference between patients pretreated with MgSO4 or placebo. CONCLUSION: Pretreatment with a single intravenous dose of MgSO4 60 mg/kg does not decrease the efficacy of recommended doses of sugammadex for the reversal of a moderate and deep neuromuscular block induced by an intubation dose of rocuronium.

How to make tonsillectomy a safer procedure: the anaesthetist's view.

Anaesthetists use specific drugs peri-operatively to try to decrease the incidence and severity of postoperative pain and of postoperative nausea and vomiting. These drugs are usually administered pre-operatively with the premedication, or intra-operatively when the patient is still anaesthetised. The aim of this approach is to prevent the occurrence of intolerable pain or to avoid any nausea or vomiting symptoms which may be clearly unpleasant for the patient and which interfere with the patient's well-being, recovery and satisfaction. However, since most of these drugs are given prophylactically, and since not all patients will actually be suffering from intolerable pain or severe nausea and vomiting symptoms postoperatively, many patients will receive these drugs unnecessarily. Thus, for the individual patient, the risk of suffering from drug-related adverse reactions without profiting from any benefit may be relevant. Perhaps a 'wait-and-see' approach should be considered; especially non-steroidal anti-inflammatory drugs or dexamethasone should not be given pre-operatively to all patients but should be provided exclusively to those in whom alternative analgesics (for instance, paracetamol combined with a weak opioid) or alternative anti-emetics (for instance, a setron or droperidol) have failed or are associated with unacceptable adverse effects. There is no evidence that prophylactic administration of an analgesic or an anti-emetic is more efficacious than the therapeutic administration. An interesting alternative to achieve satisfactory posttonsillectomy analgesia may be with local anaesthesia swabs that are applied onto the wound.

Transcutaneous nicotine does not prevent postoperative nausea and vomiting: a randomized controlled trial.

AIMS: There is empirical evidence that smokers are less likely to suffer from postoperative nausea and vomiting (PONV). We sought to investigate whether transcutaneus nicotine prevents PONV. METHODS: Non-smokers receiving general anaesthesia for surgery were randomly allocated to Nicotinell Patch 10cm(2) (TTS 10), containing 17.5mg of nicotine (average delivery rate, 7mg 24h(-1) ) or matching placebo patch. Patches were applied 1h before surgery and were left in situ until 24h after surgery (or until the first PONV symptoms occurred). RESULTS: We randomized 90 patients (45 nicotine, 45 placebo). In the post-anaesthetic care unit, the incidence of nausea was 22.2% with nicotine and 24.4% with placebo (P= 0.80), and the incidence of vomiting was 20.0% with nicotine and 17.8% with placebo (P= 0.78). Cumulative 24h incidence of nausea was 42.2% with nicotine and 40.0% with placebo (P= 0.83), and of vomiting was 31.1% with nicotine and 28.9% with placebo (P= 0.81). PONV episodes tended to occur earlier in the nicotine group. Postoperative headache occurred in 17.8% of patients treated with nicotine and in 15.6% with placebo (P= 0.49). More patients receiving nicotine reported a low quality of sleep during the first postoperative night (26.7% vs. 6.8% with placebo; P= 0.01). CONCLUSIONS: Non-smokers receiving a prophylactic nicotine patch had a similar incidence of PONV during the first 24h and tended to develop PONV symptoms earlier compared with controls. They had a significantly increased risk of insomnia during the first postoperative night.

Rapid arousal from anaesthesia after reversal of deep rocuronium-induced neuromuscular block with sugammadex in a neuroradiological procedure.

We describe the case of a 42-year-old man undergoing elective embolisation of an arteriovenous malformation at the level of the right posterior cerebral artery under propofol anaesthesia. We used the SedLine Brain Function Monitor (Masimo) to titrate the anaesthetic depth with propofol. At the end of the procedure, the patient aroused from anaesthesia very rapidly after the reversal of deep neuromuscular block with sugammadex, despite still significant calculated doses of propofol at the effect site. This rapid arousal was monitored using the SedLine Brain Function Monitor.

Genetic Susceptibility Toward Nausea and Vomiting in Surgical Patients.

Postoperative nausea and vomiting (PONV) are frequently occurring adverse effects following surgical procedures. Despite predictive risk scores and a pallet of prophylactic antiemetic treatments, it is still estimated to affect around 30% of the patients, reducing their well-being and increasing the burden of post-operative care. The aim of the current study was to characterize selected genetic risk factors of PONV to improve the identification of at risk patients. We genotyped 601 patients followed during the first 24 h after surgery for PONV symptoms in the absence of any antiemetic prophylaxis. These patients were recruited in the frame of a randomized, placebo controlled clinical study aiming to test the efficacy of dexamethasone as a treatment of established PONV. We examined the impact of selected single nucleotide polymorphisms (SNPs) located around 13 different genes and the predicted activity of 6 liver drug metabolizing enzymes from the cytochromes P450 family (CYP) on the occurrence and recurrence of PONV. Our genetic study confirms the importance of genetic variations in the type 3B serotonin receptor in the occurrence of PONV. Our modelling shows that integration of rs3782025 genotype in preoperative risk assessments may help improve the targeting of antiemetic prophylaxis towards patients at risk of PONV.

Direct thromboaspiration efficacy for mechanical thrombectomy is related to the angle of interaction between the aspiration catheter and the clot.

BACKGROUND: Direct thromboaspiration has been reported as an effective mechanical treatment for acute ischemic stroke. We aimed to determine whether the angle of interaction between the aspiration catheter and the clot affects the success of clot removal in ischemic stroke patients with large vessel occlusion in the anterior and posterior circulation. METHODS: All patients treated at our institution by direct thromboaspiration as a firstline technique between January 2016 and December 2017 were enrolled in the study. We retrospectively reviewed baseline and procedural characteristics, the angle of interaction formed between the aspiration catheter and the clot, the modified Thrombolysis in Cerebral Infarction score, and the 3 month modified Rankin Scale score. RESULTS: 85 patients underwent direct thromboaspiration as the firstline treatment during the study period. 100 direct thromboaspiration passes were performed. An angle of interaction of ≥125.5° significantly influenced the success of clot removal (P<0.001) with good sensitivity and specificity, in particular for occlusion of the middle cerebral and basilar artery. The combination of aspiration with a stent retriever based thrombectomy was a valid rescue treatment in cases of standalone direct thromboaspiration failure. CONCLUSIONS: In our series, an angle of interaction between the aspiration catheter and the clot of ≥125.5° was significantly associated with successful clot removal. The prediction of the angle of interaction on pretreatment imaging may help operators to select the most adequate mechanical thrombectomy technique on a case by case basis.

Perioperative intravenous low-dose ketamine for neuropathic pain after major lower back surgery: A randomized, placebo-controlled study.

BACKGROUND: Chronic pain after major lower back surgery is frequent. We investigated in adults the effect of perioperative low-dose ketamine on neuropathic lower back pain, assessed by the DN4 questionnaire, 6 and 12 months after major lower back surgery. METHODS: In this single-centre randomized trial, 80 patients received intravenous ketamine 0.25 mg/kg preoperatively, followed by 0.25 mg kg-1  hr-1 intraoperatively, and 0.1 mg kg-1  hr-1 from 1 hr before the end of surgery until the end of recovery room stay; 80 controls received placebo. RESULTS: Preoperatively, 47.4% of patients in the ketamine group and 46.3% in the placebo group had neuropathic pain; 10% and 3.8%, respectively, were using strong opioids. At the end of the infusion, the median cumulative dose of ketamine was 84.8 mg (IQR 67.4-106.7) and the median plasma level was 97 ng/ml (IQR 77.9-128.0). At 6 months, 28.8% of patients in the ketamine group and 23.5% in the placebo group had neuropathic pain (absolute difference, 5.2%; 95% CI -10.7 to 21.1; p = .607). At 12 months, 26.4% of patients in the ketamine group and 17.9% in the placebo group had neuropathic pain (absolute difference 8.5%; 95% CI -6.7 to 23.6; p = .319). CONCLUSIONS: In this patient population with a high prevalence of neuropathic lower back pain undergoing major lower back surgery, a perioperative intravenous low-dose ketamine infusion did not have an effect on the prevalence of neuropathic lower back pain at 6 or 12 months postoperatively. SIGNIFICANCE: We were unable to show any analgesic benefit of a short-term perioperative ketamine infusion as an adjuvant to multimodal analgesia in patients with a high prevalence of neuropathic lower back pain undergoing major back surgery. Based on these data, the widespread opinion that ketamine is universally analgesic across different pain conditions must be challenged. PRIOR PRESENTATIONS: Abstract presentation at the annual congress of the Swiss Society of Anaesthesiology, 2016, Basel, Switzerland. CLINICAL TRIAL NUMBER AND REGISTRY URL: Registered by Dr Christoph Czarnetzki as principal investigator on February 20, 2008 at clinicaltrials.gov (NCT00618423).

[Preoperative check-up of patients with neurological disease]. / Präoperative Abklärungen bei Patienten mit neurologischen Erkrankungen.

Often, patients with neurological diseases need to undergo surgical procedures. The most frequent are orthopaedic surgery (tenotomies, corrections of articulations), urological procedures (for instance, sphincter surgery for urinary incontinence), ENT surgery (tracheotomy), or plastic surgery for closure of decubitus ulcers. Preoperatively, these patients need a careful check-up including a thorough drug history. Specific diagnostic interventions may be indicated, for instance, lung functions tests in patients with muscular weakness undergoing thoracic or upper abdominal surgery. A close collaboration between general practitioner and anaesthesiologist is warranted. It cannot be excluded that symptoms of the neurological disease will deteriorate postoperatively due to anaesthesia, surgery or perioperative stress. Medication that is used to control symptoms of a neurological disease should not be stopped in the perioperative period.

Endoscopic control of gastric emptying after administration of intravenous erythromycin in an awake patient scheduled for urgent rigid bronchoscopy.

Certain interventional pulmonology procedures such as the placement of a tracheal stent or resection of stenosing tracheal tumours require rigid bronchoscopy under general anaesthesia. Unlike an endotracheal tube with a cuff, the rigid bronchoscope only partially protects the airway from bronchoaspiration. For this reason, this procedure is performed on an elective basis in fasted patients. We describe the case of a 60-year-old man with acute respiratory distress requiring emergent rigid bronchoscopy following distal migration of a tracheal stent. One hour before the procedure, the patient had eaten a full meal. Gastric emptying was accelerated by perfusion of intravenous erythromycin and verified by endoscopy with a small diameter gastric endoscope under local anaesthesia. This 1 min procedure was very well tolerated by the patient and allowed to verify with certainty that the stomach was empty. The urgent rigid bronchoscopy for stent retrieval could then be performed safely without any risk of bronchoaspiration.