The use of cannabinoids in palliating cancer-related symptoms: a narrative review.

Despite uncertain efficacy, cannabinoids and derived products are becoming increasingly used in the field of palliative care for oncologic patients. Cannabinoids chiefly include psychoactive tetrahydrocannabinol (THC) and nonpsychoactive cannabidiol (CBD). Use of and research interest in THC, CBD, and combination THC/CBD products have increased in recent years, particularly after the Agriculture Improvement Act of 2018 made cannabis plants with <0.3% THC no longer controlled substances, and many states recently legalized THC use altogether. To provide an updated review of this topic, we reviewed randomized controlled trials with >50 patients studying cannabinoid use in cancer patients. We found that THC products, including THC and THC/CBD combination products, are helpful for treating chemotherapy-induced nausea/vomiting. CBD products were not helpful for this indication. For most other studied indications (anorexia/cachexia, mood, general global symptoms), there was no convincing evidence to support widespread cannabinoid use in cancer symptom management. The evidence for treating cancer-related pain with THC/CBD products is somewhat conflicting. We conclude that, apart from using THC products to treat chemotherapy-induced nausea/vomiting, cannabinoid products should not be routinely recommended for cancer supportive care. Further research in the form of large randomized controlled trials is warranted in this area.

Neurokinin-1 receptor antagonists for the prevention of postoperative nausea and vomiting.

Despite the availability of several classes of antiemetics, postoperative nausea and vomiting (PONV) remains a substantial burden for patients following surgery, resulting in patient dissatisfaction and prolonged stays in post-anesthesia care units and ultimately increasing the cost of care. Enhanced recovery protocols and PONV management guidelines are now centered on the assessment of the individual patient's risk for developing PONV, as well as multimodal prophylaxis using antiemetics targeting different mechanisms of action. Over the last two decades, the neurokinin-1 receptor (NK1R) has emerged as a therapeutic target for the management of PONV. This review of the literature explains the role of the NK1R and its ligand-substance P-in vomiting, describes the pharmacologic and pharmacokinetic properties of NK1R antagonists (NK1RAs) and summarizes the clinical evidence supporting NK1RAs for PONV prophylaxis in patients undergoing surgery. In particular, we discuss the therapeutic application of NK1RA in PONV prophylaxis protocols owing to their advantages over other antiemetic classes in efficacy, duration of efficacy, safety, pharmacology, and ease of administration. Future studies will be aimed at further investigating the efficacy and safety of NK1RA-based multimodal combinations, particularly among vulnerable populations (e.g., children and elderly).

A Postoperative Nausea and Vomiting Update: Current information on New Drugs, Old Drugs, Rescue/Treatment, Combination Therapies and Nontraditional Modalities.

This article's objective is to present the latest evidence and information on the management of postoperative nausea and vomiting (PONV). PONV continues to affect 30% of the surgical population causing patient dissatisfaction, extending length of stay, and increasing overall costs. This review includes the introduction of 2 new intravenous formulations of antiemetics (amisulpride, aprepitant), updates on nontraditional therapies, suggestions for combination prophylaxis, emerging data on rescue treatment, and considerations for special populations and settings. Both of the new antiemetics provide promising options for pharmacologic interventions for PONV with favorable safety profiles.

Rescue Treatment of Postoperative Nausea and Vomiting: A Systematic Review of Current Clinical Evidence.

Although prophylactic antiemetics are commonly used perioperatively, an estimated 30% of surgical patients still suffer from postoperative nausea and vomiting (PONV). Very few prospective trials have studied rescue treatment of PONV after failure of prophylaxis, providing limited evidence to support clinical management. In patients who have failed PONV prophylaxis, administering a rescue antiemetic from the same drug class has been reported to be ineffective. For many antiemetics currently used in PONV rescue, significant uncertainty remains around the effective dose range, speed of onset, duration of effect, safety, and overall risk-benefit ratio. As prompt, effective PONV rescue after failure of prophylaxis is important to optimize postoperative recovery and resource utilization, we conduct this systematic review to summarize the current evidence available on the topic.

History of Respiratory Stimulants.

The interest in substances that stimulate respiration has waxed and waned throughout the years, intensifying following the introduction of a new class of drugs that causes respiratory depression, and diminishing when antidotes or better drug alternatives are found. Examples include the opioids--deaths increasing during overprescribing, diminishing with wider availability of the opioid receptor antagonist naloxone, increasing again during COVID-19; the barbiturates--until largely supplanted by the benzodiazepines; propofol; and other central nervous system depressants. Unfortunately, two new troubling phenomena force a reconsideration of the status-quo: (1) overdoses due to highly potent opioids such as fentanyl, and even more-potent licit and illicit fentanyl analogs, and (2) overdose due to polysubstance use (the combination of an opioid plus one or more non-opioid drug, such as a benzodiazepine, sedating antidepressant, skeletal muscle relaxant, or various other agents). Since these now represent the majority of cases, new solutions are again needed. An interest in respiratory stimulants has been revived. This interest can be informed by a short review of the history of this interesting class of medications. We present a short history of the trajectory of advances toward more selective and safer respiratory stimulants.

Position Paper on Critical Care Pharmacy Services (Executive Summary): 2020 Update.

OBJECTIVES: Provide a multiorganizational statement to update the statement from a paper in 2000 about critical care pharmacy practice and make recommendations for future practice. DESIGN: The Society of Critical Care Medicine, American College of Clinical Pharmacy Critical Care Practice and Research Network, and the American Society of Health-System Pharmacists convened a joint task force of 15 pharmacists representing a broad cross-section of critical care pharmacy practice and pharmacy administration, inclusive of geography, critical care practice setting, and roles. The Task Force chairs reviewed and organized primary literature, outlined topic domains, and prepared the methodology for group review and consensus. A modified Delphi method was used until consensus (>66% agreement) was reached for each practice recommendation. Previous position statement recommendations were reviewed and voted to either retain, revise, or retire. Recommendations were categorized by level of ICU service to be applicable by setting, and grouped into five domains: patient care, quality improvement, research and scholarship, training and education, and professional development. MAIN RESULTS: There are 82 recommendation statements: forty-four original recommendations and 38 new recommendation statements. Thirty-four recommendations were made for patient care, primarily relating to critical care pharmacist duties and pharmacy services. In the quality improvement domain, 21 recommendations address the role of the critical care pharmacist in patient and medication safety, clinical quality programs, and analytics. Nine recommendations were made in the domain of research and scholarship. Ten recommendations are in the domain of training and education and eight recommendations regarding professional development. CONCLUSIONS: The statements recommended by this taskforce delineate the activities of a critical care pharmacist and the scope of pharmacy services within the ICU. Effort should be made from all stakeholders to implement the recommendations provided, with continuous effort toward improving the delivery of care for critically ill patients.

Position Paper on Critical Care Pharmacy Services (Executive Summary): 2020 Update.

OBJECTIVES: Provide a multiorganizational statement to update the statement from a paper in 2000 about critical care pharmacy practice and makes recommendations for future practice. DESIGN: The Society of Critical Care Medicine, American College of Clinical Pharmacy Critical Care Practice and Research Network, and the American Society of Health-Systems Pharmacists convened a joint task force of 15 pharmacists representing a broad cross-section of critical care pharmacy practice and pharmacy administration, inclusive of geography, critical care practice setting, and roles. The Task Force chairs reviewed and organized primary literature, outlined topic domains, and prepared the methodology for group review and consensus. A modified Delphi method was used until consensus (> 66% agreement) was reached for each practice recommendation. Previous position statement recommendations were reviewed and voted to either retain, revise, or retire. Recommendations were categorized by level of ICU service to be applicable by setting, and grouped into five domains: patient care, quality improvement, research and scholarship, training and education, and professional development. MAIN RESULTS: There are 82 recommendation statements: forty-four original recommendations and 38 new recommendation statements. Thirty-four recommendations were made for patient care, primarily relating to critical care pharmacist duties and pharmacy services. In the quality improvement domain, 21 recommendations address the role of the critical care pharmacist in patient and medication safety, clinical quality programs, and analytics. Nine recommendations were made in the domain of research and scholarship. Ten recommendations are in the domain of training and education and eight recommendations regarding professional development. CONCLUSIONS: The statements recommended by this taskforce delineate the activities of a critical care pharmacist and the scope of pharmacy services within the ICU. Effort should be made from all stakeholders to implement the recommendations provided, with continuous effort toward improving the delivery of care for critically ill patients.

Position Paper on Critical Care Pharmacy Services: 2020 Update.

OBJECTIVES: To provide a multiorganizational statement to update recommendations for critical care pharmacy practice and make recommendations for future practice. A position paper outlining critical care pharmacist activities was last published in 2000. Since that time, significant changes in healthcare and critical care have occurred. DESIGN: The Society of Critical Care Medicine, American College of Clinical Pharmacy Critical Care Practice and Research Network, and the American Society of Health-Systems Pharmacists convened a joint task force of 15 pharmacists representing a broad cross-section of critical care pharmacy practice and pharmacy administration, inclusive of geography, critical care practice setting, and roles. The Task Force chairs reviewed and organized primary literature, outlined topic domains, and prepared the methodology for group review and consensus. A modified Delphi method was used until consensus (> 66% agreement) was reached for each practice recommendation. Previous position statement recommendations were reviewed and voted to either retain, revise, or retire. Recommendations were categorized by level of ICU service to be applicable by setting and grouped into five domains: patient care, quality improvement, research and scholarship, training and education, and professional development. MAIN RESULTS: There are 82 recommendation statements: 44 original recommendations and 38 new recommendation statements. Thirty-four recommendations represent the domain of patient care, primarily relating to critical care pharmacist duties and pharmacy services. In the quality improvement domain, 21 recommendations address the role of the critical care pharmacist in patient and medication safety, clinical quality programs, and analytics. Nine recommendations were made in the domain of research and scholarship. Ten recommendations were made in the domain of training and education and eight recommendations regarding professional development. CONCLUSIONS: Critical care pharmacists are essential members of the multiprofessional critical care team. The statements recommended by this taskforce delineate the activities of a critical care pharmacist and the scope of pharmacy services within the ICU. Effort should be made from all stakeholders to implement the recommendations provided, with continuous effort toward improving the delivery of care for critically ill patients.

Fourth Consensus Guidelines for the Management of Postoperative Nausea and Vomiting.

This consensus statement presents a comprehensive and evidence-based set of guidelines for the care of postoperative nausea and vomiting (PONV) in both adult and pediatric populations. The guidelines are established by an international panel of experts under the auspices of the American Society of Enhanced Recovery and Society for Ambulatory Anesthesia based on a comprehensive search and review of literature up to September 2019. The guidelines provide recommendation on identifying high-risk patients, managing baseline PONV risks, choices for prophylaxis, and rescue treatment of PONV as well as recommendations for the institutional implementation of a PONV protocol. In addition, the current guidelines focus on the evidence for newer drugs (eg, second-generation 5-hydroxytryptamine 3 [5-HT3] receptor antagonists, neurokinin 1 (NK1) receptor antagonists, and dopamine antagonists), discussion regarding the use of general multimodal PONV prophylaxis, and PONV management as part of enhanced recovery pathways. This set of guidelines have been endorsed by 23 professional societies and organizations from different disciplines (Appendix 1).Guidelines currently available include the 3 iterations of the consensus guideline we previously published, which was last updated 6 years ago; a guideline published by American Society of Health System Pharmacists in 1999; a brief discussion on PONV management as part of a comprehensive postoperative care guidelines; focused guidelines published by the Society of Obstetricians and Gynecologists of Canada, the Association of Paediatric Anaesthetists of Great Britain & Ireland and the Association of Perianesthesia Nursing; and several guidelines published in other languages.The current guideline was developed to provide perioperative practitioners with a comprehensive and up-to-date, evidence-based guidance on the risk stratification, prevention, and treatment of PONV in both adults and children. The guideline also provides guidance on the management of PONV within enhanced recovery pathways.The previous consensus guideline was published 6 years ago with a literature search updated to October 2011. Several guidelines, which have been published since, are either limited to a specific populations or do not address all aspects of PONV management. The current guideline was developed based on a systematic review of the literature published up through September 2019. This includes recent studies of newer pharmacological agents such as the second-generation 5-hydroxytryptamine 3 (5-HT3) receptor antagonists, a dopamine antagonist, neurokinin 1 (NK1) receptor antagonists as well as several novel combination therapies. In addition, it also contains an evidence-based discussion on the management of PONV in enhanced recovery pathways. We have also discussed the implementation of a general multimodal PONV prophylaxis in all at-risk surgical patients based on the consensus of the expert panel.

Snake Eyes: Coral Snake Neurotoxicity Associated With Ocular Absorption of Venom and Successful Treatment With Exotic Antivenom.

BACKGROUND: Coral snake bites from Micrurus fulvius and Micrurus tener account for < 1% of all snake bites in North America. Coral snake envenomation may cause significant neurotoxicity, including respiratory insufficiency, and its onset may be delayed up to 13 h. CASE REPORT: We present a unique patient encounter of M. tener venom exposure through the ocular mucous membranes and a small cutaneous bite, resulting in neurotoxicity. To our knowledge, this is the first reported case of systemic neurotoxicity associated with ocular contact with coral snake venom. Our patient developed rapid-onset skeletal muscle weakness, which is very uncommon for M. tener, along with cranial nerve deficits. Acquisition of antivenom was challenging, but our patient provides a rare report of resolution of suspected M. tener neurotoxicity after receiving Central American coral snake (Micrurus nigrocinctus) antivenom. Our patient subsequently developed serum sickness, a known delayed complication of antivenom. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?: The emergency physician should be aware that coral snake venom may be absorbed through different routes. Neurotoxicity and respiratory insufficiency may be fatal and onset may be delayed up to 13 h. North American Coral Snake Antivenom is in very limited supply, so non-Food and Drug Administration-approved alternative coral snake antivenoms may be used for patients demonstrating neurotoxicity. Emergency physicians should be proactive in contacting a toxicologist to procure antivenom, as well as consideration of adjunctive treatments, such as neostigmine. Furthermore, whole immunoglobulin G products, such as antivenom, may result in immediate and delayed reactions.

Incidence, risk factors, and consequences of residual neuromuscular block in the United States: The prospective, observational, multicenter RECITE-US study.

STUDY OBJECTIVE: To determine the incidence burden and associated risk factors of residual neuromuscular block (rNMB) during routine U.S. hospital care. DESIGN: Blinded multicenter cohort study. SETTING: Operating and recovery rooms of ten community and academic U.S. hospitals. PATIENTS: Two-hundred fifty-five adults, ASA PS 1-3, underwent elective abdominal surgery with general anesthesia and ≥1 dose of non-depolarizing neuromuscular blocking agent (NMBA) for endotracheal intubation and/or maintenance of NMB between August 2012 and April 2013. INTERVENTIONS: TOF measurements using acceleromyography were performed on patients already receiving routine anesthetic care for elective open or laparoscopic abdominal surgery. Measurements allowed assessment of the presence of residual neuromuscular block (rNMB), defined as a train-of-four (TOF) ratio <0.9 at tracheal extubation. We recorded patient and procedural characteristics and assessed TOF ratios (T4/T1) at various times throughout the procedure and at tracheal extubation. Differences in patient and clinical characteristics were compared using Fisher's exact test for categorical variables and t-test for continuous variables. Multivariate logistic regression assessed risk factors associated with rNMB at extubation. MAIN RESULTS: Most of the study population, 64.7% (n = 165) had rNMB (TOF ratio < 0.9), among them, 31.0% with TOF ratio <0.6. Among those receiving neostigmine and/or qualitative peripheral nerve stimulation per clinical decision, 65.0% had rNMB. After controlling for confounders, we observed male gender (odds ratio: 2.60, P = 0.008), higher BMI (odds ratio: 1.04/unit, P = 0.043), and surgery at a community hospital (odds ratio: 3.15, P = 0.006) to be independently associated with increased odds of rNMB. CONCLUSIONS: Assessing TOF ratios blinded to the care team, we found that the majority of patients (64.7%) in this study had rNMB at tracheal extubation, despite neostigmine administration and qualitative peripheral nerve stimulation used for routine clinical care. Qualitative neuromuscular monitoring and clinical judgement often fails to detect rNMB after neostigmine reversal with potential severe consequences to the patient. Our data suggests that clinical care could be improved by considering quantitative neuromuscular monitoring for routine care.

Effect of adding tetracaine to bupivacaine on duration of analgesia in supraclavicular brachial plexus nerve blocks for ambulatory shoulder surgery.

The objective of this study was to determine if the addition of 1% tetracaine to 0.25% bupivacaine prolonged the duration of postoperative analgesia of supraclavicular brachial plexus nerve blockade for patients undergoing ambulatory shoulder surgery. We conducted a prospective, double-blinded, randomized controlled clinical study at an ambulatory surgery center utilizing ultrasound- and nerve stimulation-guided supraclavicular nerve blockade for postoperative analgesia. The control group received 30 mL of 0.25% bupivacaine plus 4 mL preservative-free saline. The study group received 30 mL of 0.25% bupivacaine plus 4 mL of 1% tetracaine. Patients documented their visual analog scale scores and intake of pain medications for 3 days. Primary outcomes included time of first postoperative pain, time of first postoperative pain pill, and time of return of motor and sensory function. Secondary outcomes included pain score and pain medication intake trends and adverse events secondary to the nerve block. A total of 84 patients completed the study, 42 patients in each group. The study group was statistically significantly older than the control group (mean age, 54 vs 48 years; P = 0.04). The mean duration of analgesia was 16.6 ± 8.3 h for the control group and 17.1 ± 7.3 h for the study group (P = 0.69). No outcomes were statistically different. In conclusion, there was no significant difference in duration of postoperative analgesia with the addition of 1% tetracaine to 0.25% bupivacaine in supraclavicular brachial plexus nerve blockade. No differences were identified in postoperative pain medications, pain scores, or complications.

Consensus guidelines for the management of postoperative nausea and vomiting.

The present guidelines are the most recent data on postoperative nausea and vomiting (PONV) and an update on the 2 previous sets of guidelines published in 2003 and 2007. These guidelines were compiled by a multidisciplinary international panel of individuals with interest and expertise in PONV under the auspices of the Society for Ambulatory Anesthesia. The panel members critically and systematically evaluated the current medical literature on PONV to provide an evidence-based reference tool for the management of adults and children who are undergoing surgery and are at increased risk for PONV. These guidelines identify patients at risk for PONV in adults and children; recommend approaches for reducing baseline risks for PONV; identify the most effective antiemetic single therapy and combination therapy regimens for PONV prophylaxis, including nonpharmacologic approaches; recommend strategies for treatment of PONV when it occurs; provide an algorithm for the management of individuals at increased risk for PONV as well as steps to ensure PONV prevention and treatment are implemented in the clinical setting.

Treatment of local-anesthetic toxicity with lipid emulsion therapy.

PURPOSE: The use of lipid emulsion to treat local-anesthetic toxicity is discussed. SUMMARY: Systemic toxicity from local anesthetics is a rare but potentially fatal complication of regional anesthesia. There is increasing evidence that lipid emulsion may be an effective treatment to reverse the cardiac and neurologic effects of local-anesthetic toxicity. A literature search identified seven case reports of local-anesthetic toxicity in which lipid emulsion was used. Lipid emulsion was found to be successful in the treatment of local-anesthetic toxicity associated with various regional anesthetic techniques and multiple local anesthetics. The majority of patients in the case reports reviewed were unresponsive to initial management of local-anesthetic toxicity with standard resuscitative measures, but all recovered completely after receiving lipid emulsion therapy. The initial dose of lipid emulsion administered varied among the case reports, as well as whether a lipid emulsion infusion was started and at what point during resuscitation. Based on the case reports reviewed, an initial bolus dose of 1.5 mL/kg followed by an infusion of 10 mL/min as soon as local-anesthetic toxicity is suspected seems most beneficial. The pharmacokinetics of lipid emulsion therapy in the treatment of local-anesthetic toxicity has not been fully elucidated but likely involves increasing metabolism, distribution, or partitioning of the local anesthetic away from receptors into lipid within tissues. CONCLUSION: Lipid emulsion has been reported useful in the treatment of systemic toxicity caused by local anesthetics. The mechanism of effect is unclear, and evidence for the benefit of lipid therapy in humans is from case reports only.

Complementary/alternative medicine use among chronic pain clinic patients.

Complementary and alternative therapies have enjoyed increasingly widespread use in recent years. Because of this trend, we were eager to obtain a better grasp on the actual number of people in our hospital's pain clinic who have used these modalities. In an effort to explore the use of complementary/alternative medicine (CAM) by patients seen in an anesthesiology chronic pain clinic, we conducted a study using a questionnaire. This questionnaire contained two sections, one covering complementary/alternative modalities and the other dealing with herbals or nutraceuticals. More than 400 patients were surveyed, 41% of whom were male and 59% of whom were female. Comparing alternative therapies by gender revealed no statistical difference in males versus females. The most commonly chosen modalities overall were nutraceuticals, massage therapy, and acupuncture. In terms of age, we found that the patients surveyed who were older than 60 years of age preferred nutraceuticals, and that the younger age group preferred more interactive relaxation techniques, such as meditation and massage.