A Descriptive Analysis of Adverse Event Reports from the Quebec Cannabis Registry.

INTRODUCTION: Published data on the safety of natural medical cannabis (MC) when used in the real-world clinical practice setting are lacking. This study aimed to describe adverse events (AEs) reported across three years following MC initiation. METHODS: The Quebec Cannabis Registry (QCR) was a prospective registry of adults enrolled through participating physicians when they initiated MC between May 2015 and October 2018. Follow-up ended at MC discontinuation, loss to follow-up, three years, or end of data collection (May 2019). Data were collected at baseline and at follow-up visits every three months for the first two years, then once in the third year. Physicians filled adverse event (AE) reports, which were coded using MedDRA® preferred terms (PTs), and descriptive analyses were conducted. RESULTS: A total of 2991 patients were enrolled (mean age 50.9 years, 50.2% females). During follow-up, 108 patients (3.6%) experienced moderate or severe AEs, yielding 111 AE reports (three patients had two reports) and 214 AEs (average 1.9 AEs per report). Mild AEs were recorded as a reason for MC discontinuation for nine patients, but no AE reports were available. The most common PTs for ingested MC (62 reports) were dizziness (12.9%), nausea (11.3%), somnolence (9.7%), and vomiting (8.1%), and for inhaled MC (23 reports), headache (13.0%) was the most common. The most frequent PTs associated with tetrahydrocannabinol (THC)-dominant MC (25 reports) were dizziness and somnolence (12.0% each); for cannabidiol (CBD)-dominant MC (20 reports), vomiting (20.0%) was most common; and dizziness (17.2%), nausea (13.8%), somnolence (10.3%), and headache (8.6%) were the most frequent for balanced MC (58 reports). CONCLUSION: No new safety concerns were identified relative to the published literature, although notable differences in AE profile between modes of administration and cannabinoid content ratios should be considered by health professionals. Further work identifying and managing risk factors for AEs is warranted to maintain a favorable benefit-risk balance for MC.

Efficacy of a propofol bolus against placebo to prevent cough at emergence from general anesthesia with desflurane: a randomized controlled trial.

PURPOSE: Emergence from anesthesia is a critical period and cough can result in adverse effects. Propofol inhibits airway reflexes and when infused it reduces cough more than inhalation anesthesia does. We evaluated the effect of a propofol bolus given at emergence on the incidence of coughing following a desflurane-based anesthesia. METHODS: One hundred and fifty-four patients scheduled for elective surgery were prospectively randomized to propofol (0.5 mg·kg-1) or normal saline (NS) administered at the end of the surgery at 1 minimum alveolar concentration (MAC) of desflurane. A "no touch" emergence technique was used until extubation. The primary outcome was the incidence of cough at the discontinuation of desflurane (T0) and reaching a MAC adjusted for age (MACage) of 0.15. Secondary outcomes included incidence and severity of cough until five minutes postextubation (T0-T5), time to extubation, nausea and vomiting, sedation, hemodynamic variations, postoperative hypoventilation, hypoxemia, and sore throat. RESULTS: We could not draw inferences on the incidence of cough between T0 and MACage of 0.15 because only 27/68 (40%) patients in the NS group and 13/73 (18%) patients in the propofol group regained consciousness before reaching a MACage of 0.15. There were no significant differences between the groups in coughing incidence and severity between T0 and T5 (NS group, 57/68 [84%] vs propofol group, 70/73 [96%] ). The mean time to extubation in the propofol group was prolonged by 3 min 27 sec (95% confidence interval, 1 min 7 sec to 4 min 47 sec; P < 0.001) and more vasopressors were used at emergence (P = 0.02). The incidence of respiratory complications, nausea and vomiting, agitation, and sedation were not different between groups. CONCLUSION: In the present trial, a propofol bolus administered at emergence did not reduce the incidence of cough occurring between T0 and T5 following a desflurane-based general anesthesia compared with placebo. TRIAL REGISTRATION: ClinicalTrials.gov (NCT02932397); registered 13 October 2016.

RéSUMé: OBJECTIF: L'émergence de l'anesthésie est une période critique et la toux peut entraîner des effets indésirables. Le propofol inhibe les réflexes des voies aériennes et, lorsqu'il est perfusé, il est plus efficace pour réduire la toux que l'anesthésie inhalée. Nous avons évalué l'effet d'un bolus de propofol administré à l'émergence sur l'incidence de toux après une anesthésie à base de desflurane. MéTHODE: Cent cinquante-quatre patients devant bénéficier d'une chirurgie non urgente ont été randomisés prospectivement à recevoir du propofol (0,5 mg·kg−1) ou une solution physiologique de sérum salé (NS) administrée à la fin de la chirurgie lorsque la concentration alvéolaire minimale (MAC) de desflurane était de 1. Une technique d'émergence « sans contact ¼ a été utilisée jusqu'à l'extubation. Le critère d'évaluation principal était l'incidence de toux à l'arrêt du desflurane (T0) et à l'atteinte d'une MAC ajustée en fonction de l'âge (MACâge) de 0,15. Les critères d'évaluation secondaires comprenaient l'incidence et la gravité de la toux jusqu'à cinq minutes après l'extubation (T0-T5), le délai d'extubation, les nausées et vomissements, la sédation, les variations hémodynamiques, l'hypoventilation postopératoire, l'hypoxémie et les maux de gorge. RéSULTATS: Nous n'avons pas pu tirer de conclusions sur l'incidence de toux entre T0 et à une MACâge de 0,15 parce que seulement 27/68 (40 %) patients du groupe NS et 13/73 (18 %) patients du groupe propofol ont repris conscience avant d'atteindre une MACâge de 0,15. Il n'y avait aucune différence significative entre les groupes dans l'incidence et la gravité de la toux entre T0 et T5 (groupe NS, 57/68 [84 %] vs groupe propofol, 70/73 [96 %]). Le temps moyen d'extubation dans le groupe propofol a été prolongé de 3 min 27 sec (intervalle de confiance à 95 %, 1 min 7 sec à 4 min 47 sec; P < 0,001) et une plus grande quantité de vasopresseurs a été utilisée à l'émergence (P = 0,02). L'incidence de complications respiratoires, de nausées et vomissements, d'agitation, et de sédation n'était pas différente entre les groupes. CONCLUSION: Dans la présente étude, un bolus de propofol administré à l'émergence n'a pas réduit l'incidence de toux survenant entre T0 et T5 après une anesthésie générale à base de desflurane par rapport au placebo. ENREGISTREMENT DE L'éTUDE: ClinicalTrials.gov (NCT02932397); enregistrée le 13 octobre 2016.

Predictors of Pain Reduction Among Fibromyalgia Patients Using Medical Cannabis: A Long-Term Prospective Cohort Study.

OBJECTIVE: Many patients with fibromyalgia (FM) report using cannabis as a strategy to improve pain. Given that pain often co-occurs with symptoms of anxiety and depression (i.e., negative affect) and sleep problems among patients with FM, improvements in these symptoms might indirectly contribute to reductions in pain intensity following cannabis use. The main objective of the study was to examine whether changes in pain intensity following initiation of medical cannabis among patients with FM could be attributed to concurrent changes (i.e., reductions) in negative affect and sleep problems. METHODS: This was a 12-month prospective cohort study among patients with FM (n = 323) initiating medical cannabis under the care of physicians. Patients were assessed at baseline, and follow-up assessment visits occurred every 3 months after initiation of medical cannabis. Patients' levels of pain intensity, negative affect, and sleep problems were assessed across all visits. RESULTS: Multilevel mediation analyses indicated that reductions in patients' levels of pain intensity were partly explained by concurrent reductions in sleep problems and negative affect (both P < 0.001). This remained significant even when accounting for patients' baseline characteristics or changes in medical cannabis directives over time (all P > 0.05). CONCLUSION: Our findings provide preliminary insight into the potential mechanisms of action underlying pain reductions among patients with FM who are using medical cannabis. Given the high attrition rate (i.e., 75%) observed in the present study at 12 months, our findings cannot be generalized to all patients with FM who are using medical cannabis.

The Quebec Cannabis Registry: Investigating the Safety and Effectiveness of Medical Cannabis.

Objective: To investigate the safety and effectiveness of medical cannabis (MC) in the real-world clinical practice setting. Design: A 4-year prospective noncomparative registry of adult patients who initiated MC for a variety of indications. This paper reports on patients followed for up to 12 months, with interim visits at 3, 6, and 9 months after enrollment. Setting: Public or private outpatient clinics certified to authorize MC in the province of Quebec, Canada. Participants: Overall, 2991 adult (age ≥18 years) patients (mean age 51 years; 50.2% women) were enrolled between May 2015 and October 2018, with the last follow-up ending in May 2019. Interventions/Exposures: Cannabis products (dried, oil, or other) purchased from a Canadian licensed cannabis producer as authorized by physicians. Main Outcome Measures: The primary outcomes were self-reported pain severity, interference and relief (Brief Pain Inventory [BPI]), symptoms using the Revised Edmonton Symptom Assessment System (ESAS-r) and health-related quality of life dimensions (EQ-5D-5L) at baseline and each follow-up visit. The secondary outcomes were self-reported adverse events (AEs) and characteristics of cannabis treatment. Results: All patient-reported outcomes (BPI, ESAS-r, and EQ-5D-5L) showed a statistically significant improvement at 3 months (all p<0.01), which was maintained or further improved (for pain interference, tiredness, and well-being) over the remainder of the 12-month follow-up. Results also revealed clinically significant improvements in pain interference and tiredness, anxiety, and well-being from baseline. There were 79 AE reports (77 patients), 16 met the regulatory definition of seriousness, in which only 8 AEs were certainly or probably related to MC. Conclusions: MC directed by physicians appears to be safe and effective within 3 months of initiation for a variety of medical indications.

Postoperative outcomes in surgical COVID-19 patients: a multicenter cohort study.

BACKGROUND: Data on postoperative outcomes of the COVID-19 patient population is limited. We described COVID-19 patients who underwent a surgery and the pandemic impact on surgical activities. METHODS: We conducted a multicenter cohort study between March 13 and June 192,020. We included all COVID-19 patients who underwent surgery in nine centres of the Province of Québec, the Canadian province most afflicted by the pandemic. We also included concomitant suspected COVID-19 (subsequently confirmed not to have COVID-19) patients and patients who had recovered from it. We collected data on baseline characteristics, postoperative complications and postoperative mortality. Our primary outcome was 30-day mortality. We also collected data on overall surgical activities during this first wave and during the same period in 2019. RESULTS: We included 44 COVID-19 patients, 18 suspected patients, and 18 patients who had recovered from COVID-19 at time of surgery. Among the 44 COVID-19 patients, 31 surgeries (71%) were urgent and 16 (36%) were major. In these patients, pulmonary complications were frequent (25%) and 30-day mortality was high (15.9%). This mortality was higher in patients with symptoms (23.1%) compared to those without symptoms (5.6%), although not statistically significant (p = 0.118). Of the total 22,616 cases performed among participating centres during the study period, only 0.19% had COVID-19 at the time of surgery. Fewer procedures were performed during the study period compared to the same period in 2019 (44,486 cases). CONCLUSION: In this Canadian cohort study, postoperative 30-day mortality in COVID-19 patients undergoing surgery was high (15.9%). Although few surgeries were performed on COVID-19 patients, the pandemic impact on surgical activity volume was important. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT04458337 .

[PECS I block for postoperative analgesia in patients undergoing breast augmentation surgery: a randomized double-blind placebo-controlled study]. / Bloqueio PECS I para analgesia pós­operatória em pacientes submetidos a mamoplastia de aumento: estudo randomizado, duplo­cego, controlado por placebo.

BACKGROUND AND OBJECTIVES: PECS I block was first described for surgery involving the pectoralis muscles. No randomized clinical trial has been conducted on surgeries that directly involve these muscles, such as subpectoral breast augmentation. We hypothesized that PECS I block would decrease pain in the postoperative period in this population. METHODS: This was a randomized, double-blind, placebo-controlled trial in women undergoing subpectoral breast augmentation surgery. PECS I block was performed using 0.4 mL.kg-1 of 0.9% saline on one side and bupivacaine (0.25%) on the other side, each patient being her own control. Numeric Rating Scale (NRS) pain scores (0-10) were measured at rest and during movement. The primary outcome was pain score at rest 30 minutes after arrival in the PACU. To detect a clinically significant difference of 50% in pain reduction, 14 volunteers were enrolled (power of 90% and alpha<0.05). RESULTS: In the PACU, three patients had no difference in pain between sides, five had reduced pain on the placebo side, and six had reduced pain on the bupivacaine side. In the bupivacaine group, pain scores at rest at 5, 30 and 60 minutes and 24 hours were 4.89 (4.23-5.56; mean 95% CI), 3.75 (3.13-4.37), 3.79 (2.93-4.64), and 2.29 (1.56-3.01), respectively, whereas in the placebo group, they were 4.96 (4.32-5.60), 4.00 (3.50-4.49), 3.93 (3.12-4.73), and 2.29 (1.56-3.01), respectively. CONCLUSIONS: PECS I block in patients undergoing breast augmentation surgery does not provide better pain relief than placebo. Therefore, the indications for PECS I block in breast augmentation surgery should be reconsidered.

PECS I block for postoperative analgesia in patients undergoing breast augmentation surgery: a randomized double-blind placebo-controlled study / Bloqueio PECS I para analgesia pós-operatória em pacientes submetidos a mamoplastia de aumento: estudo randomizado, duplo-cego, controlado por placebo

Abstract Background and objectives: PECS I block was first described for surgery involving the pectoralis muscles. No randomized clinical trial has been conducted on surgeries that directly involve these muscles, such as subpectoral breast augmentation. We hypothesized that PECS I block would decrease pain in the postoperative period in this population. Methods: This was a randomized, double-blind, placebo-controlled trial in women undergoing subpectoral breast augmentation surgery. PECS I block was performed using 0.4 mL.kg-1 of 0.9% saline on one side and bupivacaine (0.25%) on the other side, each patient being her own control. Numeric Rating Scale (NRS) pain scores (0 - 10) were measured at rest and during movement. The primary outcome was pain score at rest 30 minutes after arrival in the PACU. To detect a clinically significant difference of 50% in pain reduction, 14 volunteers were enrolled (power of 90% and alpha < 0.05). Results: In the PACU, three patients had no difference in pain between sides, five had reduced pain on the placebo side, and six had reduced pain on the bupivacaine side. In the bupivacaine group, pain scores at rest at 5, 30 and 60 minutes and 24 hours were 4.89 (4.23 - 5.56; mean 95% CI), 3.75 (3.13 - 4.37), 3.79 (2.93 - 4.64), and 2.29 (1.56 - 3.01), respectively, whereas in the placebo group, they were 4.96 (4.32 - 5.60), 4.00 (3.50 - 4.49), 3.93 (3.12 - 4.73), and 2.29 (1.56 - 3.01), respectively. Conclusions: PECS I block in patients undergoing breast augmentation surgery does not provide better pain relief than placebo. Therefore, the indications for PECS I block in breast augmentation surgery should be reconsidered.

Resumo Justificativa e objetivos: O bloqueio PECS I foi descrito pela primeira vez para cirurgia envolvendo os músculos peitorais. Nenhum estudo clínico randomizado foi realizado em procedimentos envolvendo diretamente os músculos peitorais, como a mamoplastia de aumento submuscular. Nossa hipótese foi de que o bloqueio PECS I diminuiria a dor pós-operatória nessa população. Método: Realizamos estudo randomizado, duplo-cego, controlado por placebo em mulheres submetidas à mamoplastia de aumento submuscular. Realizamos o bloqueio PECS I com 0,4 mL.kg-1 de solução salina a 0,9% de um lado e bupivacaína (0,25%) do outro lado, sendo cada paciente seu próprio controle. Os escores da Escala de Avaliação Numérica (EAN) de dor (0 - 10) foram obtidos em repouso e durante movimento. O desfecho primário foi o escore de dor em repouso 30 minutos após a chegada à SRPA. Para detectar uma diferença clinicamente significante de 50% na redução da dor, 14 voluntárias foram incluídas (poder de 90% e alfa < 0,05). Resultados: Na SRPA, três pacientes não apresentaram diferença na dor entre os lados, cinco relataram menos dor no lado do placebo e seis, menos dor no lado da bupivacaína. No grupo bupivacaína, os escores de dor em repouso aos 5, 30 e 60 minutos e 24 horas foram 4,89 (4,23 - 5,56; IC médio 95%), 3,75 (3,13 - 4,37), 3,79 (2,93 - 4,64) e 2,29 (1,56 - 3,01), respectivamente, enquanto no grupo placebo foram 4,96 (4,32 - 5,60), 4,00 (3,50 - 4,49), 3,93 (3,12 - 4,73) e 2,29 (1,56 - 3,01), respectivamente. Conclusões: O bloqueio PECS I em pacientes submetidas a mamoplastia de aumento não oferece melhor alívio da dor do que o placebo. Portanto, as indicações para bloqueio de PECS I na cirurgia de aumento de mama devem ser reconsideradas.

Relative frequency and risk factors for long-term opioid therapy following surgery and trauma among adults: a systematic review protocol.

BACKGROUND: When patients have been on opioid therapy for more than 90 days, more than half of them continue using opioids years later. Knowing that long-term opioid consumption could lead to harmful side effects including misuse, abuse, and addiction, it is important to understand the risks of transitioning to prolonged opioid therapy to reduce its occurrence. Perioperative and trauma contexts are ideal models commonly used to study such transition. Long-term use of opioids might be associated with transformation of acute pain to chronic, which might be an example of a risk factor. The objectives of this knowledge synthesis are to examine the relative frequency and the risk factors for transitioning to long-term opioid therapy among patients who have undergone a surgical procedure or experienced a trauma. METHODS: The proposed study methodology is based on Preferred ReportIng Systematic Reviews and Meta-Analysis Protocols (PRISMA-P) statements on the conduct of systematic review and meta-analysis, the MOOSE Guidelines for Meta-Analyses and Systematic Reviews of Observational Studies, and the Cochrane Handbook for Systematic Review of Interventions. A systematic literature search will include multiple databases: Cochrane Central, EMBASE, MEDLINE, PsycINFO, CINHAL, PubMed, and the grey literature. We will identify studies related to opioid use beyond acute/subacute pain control after surgery or trauma. Two of the reviewers will screen all retrieved articles for eligibility and data extraction then critically appraise all identified studies. We will compile a narrative synthesis of all results and conduct a meta-analysis when feasible. As available data permits, we will perform a subgroup analysis of vulnerable populations. DISCUSSION: This systematic review will contribute to the prevention and harm reduction strategies associated with prescription opioids by identifying risk factors leading to the unwarranted long-term opioid therapy. The identification of common risk factors for long-term opioid therapy will help to orient further research on pain management as well as offer key therapeutic targets for the development of strategies to prevent prolonged opioid use. SYSTEMATIC REVIEW REGISTRATION: This protocol was registered in PROSPERO on March 2, 2018; registration number CRD42012018089907 .

Pectoral I Block Does Not Improve Postoperative Analgesia After Breast Cancer Surgery: A Randomized, Double-Blind, Dual-Centered Controlled Trial.

BACKGROUND AND OBJECTIVES: General anesthesia for breast surgery may be supplemented by using a regional anesthetic technique. We evaluated the efficacy of the first pectoral nerve block (Pecs I) in treating postoperative pain after breast cancer surgery. METHODS: A randomized, double-blind, dual-centered, placebo-controlled trial was performed. One hundred twenty-eight patients scheduled for unilateral breast cancer surgery were recruited. A multimodal analgesic regimen and surgeon-administered local anesthetic infiltration were used for all patients. Ultrasound-guided Pecs I was performed using bupivacaine or saline. The primary outcome was the patient pain score (numerical rating scale [NRS]) in the recovery unit 30 minutes after admission or just before the morphine administration (NRS ≥4/10). The secondary outcomes were postoperative opioid consumption (ie, in the recovery unit and after 24 hours). RESULTS: During recovery, no significant difference in NRS was observed between the bupivacaine (n = 62, 3.0 [1.0-4.0]) and placebo (n = 65, 3.0 [1.0-5.0]) groups (P = 0.55). However, the NRS was statistically significantly different, although not clinically significant, for patients undergoing major surgeries (mastectomies or tumorectomies with axillary clearance) (n = 29, 3.0 [0.0-4.0] vs 4.0 [2.0-5.0], P = 0.04). Morphine consumption during recovery did not differ (1.5 mg [0.0-6.0 mg] vs 3.0 mg [0.0-6.0 mg], P = 0.20), except in the major surgery subgroup (1.5 mg [0.0-6.0 mg] vs 6.0 mg [0.0-12.0 mg], P = 0.016). Intraoperative sufentanil and cumulative morphine consumption up to 24 hours did not differ between the 2 groups. Three patients experienced complications related to the Pecs I. CONCLUSIONS: Pecs I is not better than a saline placebo in the presence of multimodal analgesia for breast cancer surgery. However, its role in extended (major) breast surgery may warrant further investigation. CLINICAL TRIAL REGISTRATION: This study was registered at ClinicalTrials.gov, identifier NCT01670448.

Pectoral nerves I block is associated with a significant motor blockade with no dermatomal sensory changes: a prospective volunteer randomized-controlled double-blind study.

PURPOSE: The pectoral nerves (PECS) I block, first described in 2011 for surgery involving the pectoralis muscle, has principally been used for breast cancer surgery. No formal evaluation of its differential motor- and sensory-blocking abilities has been reported. We hypothesize that the PECS I block will produce a motor block of the pectoralis muscles with diminished upper limb adduction strength as measured with a handheld dynamometer. METHODS: We conducted a PECS I block in a randomized placebo-controlled trial in six healthy subjects who received 0.4 mL·kg-1 of 0.9% saline (placebo) on one side and bupivacaine (0.25% with 1:400 000 epinephrine) on the other. We measured both upper limb adduction strength with a dynamometer and sensory skin levels over the thorax. RESULTS: The mean (standard deviation [SD]) adductor strength evaluated before the block was 119.4 (20.7) Newtons (N). After the PECS I block with bupivacaine, the mean (SD) strength of 54.2 (16.3) N was compared with 116.0 (30.4) N in the placebo group (difference in means 61.8 N; 95% confidence interval [CI], 27.8 to 95.8 N; P = 0.005), showing a 54.6% (95% CI, 43.6 to 65.6%) reduction in adductor strength. There was no difference in dermatomal skin sensory testing between the placebo and bupivacaine sides. CONCLUSIONS: This study shows that a PECS I block produces motor blockade as shown by reduced upper limb adductor strength without any overlying dermatomal sensory loss. TRIAL REGISTRATION: www.clinicaltrials.gov (NCT03040167) 2 February 2017.

Anesthetic implications of recreational drug use.

PURPOSE: As the use of recreational drugs increases, the likelihood of an anesthesiologist perioperatively encountering patients using or addicted to these drugs will also increase. PRINCIPAL FINDINGS: Addicted patients may present for anesthetic care in a variety of circumstances in everyday elective surgeries or in acute or life-saving situations, such as emergency Cesarean delivery or trauma surgery. Therefore, it is important for anesthesiologists to know about the most common illicit drugs being used, their clinical presentation and side effects, and the anesthetic options that are beneficial or detrimental to these patients. The most frequently used illicit substances, apart from alcohol and tobacco, are cannabis, cocaine, heroin, prescription opioids, methamphetamine, and hallucinogens. When planning anesthetic care, it is important for anesthesiologists to understand the effects of these agents, including various drug interactions, to predict tolerance to some anesthetic agents, to recognize drug withdrawal signs and symptoms, and to be prepared to manage all these factors in the perioperative period. CONCLUSIONS: For optimal patient care through the perioperative period, it is critical to obtain information about patient drug use and other associated treatment in order to construct an appropriate anesthetic plan, including specific considerations during surgery, emergence, and in the postanesthesia care unit.

Postoperative awake paralysis in the intensive care unit after cardiac surgery due to residual neuromuscular blockade: a case report and prospective observational study.

PURPOSE: We report a case of awake paralysis due to residual neuromuscular blockade (NMB) in the intensive care unit (ICU) in a patient following fast-track cardiac surgery. As a result of this case, we performed a prospective quality assurance audit to investigate the incidence of residual paralysis in the ICU in a similar population of cardiac surgery patients. CLINICAL FEATURES AND AUDIT METHODS: A 73-yr-old woman (69 kg) underwent coronary artery bypass surgery under anesthesia induced with intravenous sufentanil 25 µg, midazolam 5 mg, ketamine 25 mg, and rocuronium 100 mg (followed by two additional 50-mg doses during surgery) and maintained with sevoflurane. Postoperatively in the ICU, the patient was initially sedated with propofol (50 mg·hr(-1)) but failed to awaken 90 min after its cessation. As train-of-four neurostimulation showed residual paralysis, she was re-sedated. Neostigmine 3 mg and glycopyrrolate 0.6 mg were administered, and she was extubated 30 min later. During this episode of residual paralysis, the patient was conscious and reported explicit memory of the events. She was discharged on day 7 without psychological distress related to her postoperative awake paralysis. We subsequently performed a prospective audit in 50 consecutive patients to determine the timing of NMB dosing and to quantify the incidence of residual paralysis after fast-track cardiac surgery. RESULTS: Of the 50 patients studied, 24 (48%) had received an NMB during the last hour of surgery and 33 (66%) had evidence of residual paralysis during the immediate postoperative period. CONCLUSION: Postoperative residual paralysis after fast-track cardiac surgery was common in our institution and likely contributed to the reported case of postoperative awake paralysis. We suggest that an NMB not be administered after intubation in fast-track patients. If given, however, it must be well communicated to the ICU team upon ICU admission. We further recommend routine assessment of neuromuscular function before sedation is weaned prior to extubation.

Medical cannabis: considerations for the anesthesiologist and pain physician.

PURPOSE: New regulations are in place at the federal and provincial levels in Canada regarding the way medical cannabis is to be controlled. We present them together with guidance for the safe use of medical cannabis and recent clinical trials on cannabis and pain. SOURCE: The new Canadian regulations on the use of medical cannabis, the provincial regulations, and the various cannabis products available from the Canadian Licensed Producers were reviewed from Health Canada, provincial licensing authorities, and the licensed producers website, respectively. Recent clinical trials on cannabis and pain were reviewed from the existing literature. PRINCIPAL FINDINGS: Health Canada has approved a new regulation on medical marijuana/cannabis, the Marihuana for Medical Purposes Regulations: The production of medical cannabis by individuals is illegal. Health Canada, however, has licensed authorized producers across the country, limiting the production to specific licenses of certain cannabis products. There are currently 26 authorized licensed producers from seven Canadian provinces offering more than 200 strains of marijuana. We provide guidance for the safe use of medical cannabis. The recent literature indicates that currently available cannabinoids are modestly effective analgesics that provide a safe, reasonable therapeutic option for managing chronic non-cancer-related pain. CONCLUSION: The science of medical cannabis and the need for education of healthcare professionals and patients require continued effort. Although cannabinoids work to decrease pain, there is still a need to confirm these beneficial effects clinically and to exploit them with acceptable benefit-to-risk ratios.

Multi-parameter optimization of aza-follow-ups to BI 207524, a thumb pocket 1 HCV NS5B polymerase inhibitor. Part 2: Impact of lipophilicity on promiscuity and in vivo toxicity.

We describe our efforts to identify analogs of thumb pocket 1 HCV NS5B inhibitor 1 (aza-analog of BI 207524) with improved plasma to liver partitioning and a predicted human half-life consistent with achieving a strong antiviral effect at a reasonable dose in HCV-infected patients. Compounds 3 and 7 were identified that met these criteria but exhibited off-target promiscuity in an in vitro pharmacology screen and in vivo toxicity in rats. High lipophilicity in this class was found to correlate with increased probability for promiscuous behavior and toxicity. The synthesis of an 8×11 matrix of analogs allowed the identification of C3, an inhibitor that displayed comparable potency to 1, improved partitioning to the liver and reduced lipophilicity. Although C3 displayed reduced propensity for in vitro off-target inhibition and the toxicity profile in rats was improved, the predicted human half-life of this compound was short, resulting in unacceptable dosing requirements to maintain a strong antiviral effect in patients.

Aza follow-ups to BI 207524, a thumb pocket 1 HCV NS5B polymerase inhibitor. Part 1: Mitigating the genotoxic liability of an aniline metabolite.

A series of heterocyclic aza-analogs of BI 207524 (2), a potent HCV NS5B polymerase thumb pocket 1 inhibitor, was investigated with the goal to reduce the liability associated with the release of a genotoxic aniline metabolite in vivo. Analog 4, containing a 2-aminopyridine aniline isostere that is negative in the Ames test was identified, and was found to provide comparable GT1a/1b potency to 2. Although the cross-species PK profile, poor predicted human liver distribution of analog 4 and allometry principles projected high doses to achieve a strong antiviral response in patients, this work has provided a path forward toward the design of novel thumb pocket 1 NS5B polymerase inhibitors with improved safety profiles.