Use of herbal medication in the perioperative period: Potential adverse drug interactions.

Use of herbal medications and supplements has experienced immense growth over the last two decades, with retail sales in the USA exceeding $13 billion in 2021. Since the Dietary Supplement Health and Education Act (DSHEA) of 1994 reduced FDA oversight, these products have become less regulated. Data from 2012 shows 18% of U.S. adults used non-vitamin, non-mineral natural products. Prevalence varies regionally, with higher use in Western states. Among preoperative patients, the most commonly used herbal medications included garlic, ginseng, ginkgo, St. John's wort, and echinacea. However, 50-70% of surgical patients fail to disclose their use of herbal medications to their physicians, and most fail to discontinue them preoperatively. Since herbal medications can interact with anesthetic medications administered during surgery, the American Society of Anesthesiologists (ASA) and the American Association of Nurse Anesthetists (AANA) recommend stopping herbal medications 1-2 weeks before elective surgical procedures. Potential adverse drug effects related to preoperative use of herbal medications involve the coagulation system (e.g., increasing the risk of perioperative bleeding), the cardiovascular system (e.g., arrhythmias, hypotension, hypertension), the central nervous system (e.g., sedation, confusion, seizures), pulmonary (e.g., coughing, bronchospasm), renal (e.g., diuresis) and endocrine-metabolic (e.g., hepatic dysfunction, altered metabolism of anesthetic drugs). During the preoperative evaluation, anesthesiologists should inquire about the use of herbal medications to anticipate potential adverse drug interactions during the perioperative period.

Selective Inhibition of NaV1.8 with VX-548 for Acute Pain.

BACKGROUND: The NaV1.8 voltage-gated sodium channel, expressed in peripheral nociceptive neurons, plays a role in transmitting nociceptive signals. The effect of VX-548, an oral, highly selective inhibitor of NaV1.8, on control of acute pain is being studied. METHODS: After establishing the selectivity of VX-548 for NaV1.8 inhibition in vitro, we conducted two phase 2 trials involving participants with acute pain after abdominoplasty or bunionectomy. In the abdominoplasty trial, participants were randomly assigned in a 1:1:1:1 ratio to receive one of the following over a 48-hour period: a 100-mg oral loading dose of VX-548, followed by a 50-mg maintenance dose every 12 hours (the high-dose group); a 60-mg loading dose of VX-548, followed by a 30-mg maintenance dose every 12 hours (the middle-dose group); hydrocodone bitartrate-acetaminophen (5 mg of hydrocodone bitartrate and 325 mg of acetaminophen every 6 hours); or oral placebo every 6 hours. In the bunionectomy trial, participants were randomly assigned in a 2:2:1:2:2 ratio to receive one of the following over a 48-hour treatment period: oral high-dose VX-548; middle-dose VX-548; low-dose VX-548 (a 20-mg loading dose, followed by a 10-mg maintenance dose every 12 hours); oral hydrocodone bitartrate-acetaminophen (5 mg of hydrocodone bitartrate and 325 mg of acetaminophen every 6 hours); or oral placebo every 6 hours. The primary end point was the time-weighted sum of the pain-intensity difference (SPID) over the 48-hour period (SPID48), a measure derived from the score on the Numeric Pain Rating Scale (range, 0 to 10; higher scores indicate greater pain) at 19 time points after the first dose of VX-548 or placebo. The main analysis compared each dose of VX-548 with placebo. RESULTS: A total of 303 participants were enrolled in the abdominoplasty trial and 274 in the bunionectomy trial. The least-squares mean difference between the high-dose VX-548 and placebo groups in the time-weighted SPID48 was 37.8 (95% confidence interval [CI], 9.2 to 66.4) after abdominoplasty and 36.8 (95% CI, 4.6 to 69.0) after bunionectomy. In both trials, participants who received lower doses of VX-548 had results similar to those with placebo. Headache and constipation were common adverse events with VX-548. CONCLUSIONS: As compared with placebo, VX-548 at the highest dose, but not at lower doses, reduced acute pain over a period of 48 hours after abdominoplasty or bunionectomy. VX-548 was associated with adverse events that were mild to moderate in severity. (Funded by Vertex Pharmaceuticals; VX21-548-101 and VX21-548-102 ClinicalTrials.gov numbers, NCT04977336 and NCT05034952.).

Impact of chronic medications in the perioperative period -anesthetic implications (Part II).

Background: This review article discusses the pharmacodynamic effects of the most commonly used chronic medications by patients undergoing elective surgical procedures, namely cardiovascular drugs (e.g., beta blockers, alpha-2 agonist, calcium channel blockers, ACE inhibitors, diuretics, etc.), lipid-lowering drugs, gastrointestinal medications (H2-blockers, proton pump inhibitors), pulmonary medications (inhaled ß-agonists, anticholinergics,), antibiotics (tetracyclines, clindamycin and macrolide, linezolid.), opioids and non-opioids analgesics (NSAIDs, COX-2 inhibitors, acetaminophen), gabapentanoids, erectile dysfunction (ED) drugs, psychotropic drugs (tricyclic antidepressants [TCAs], monoamine oxidase inhibitors [MAOI], selective serotonin reuptake inhibitors [SSRIs], serotonin norepinephrine reuptake inhibitors [SNRIs], and cannabinol-containing drugs).  In addition, the potential adverse drug-interactions between these chronic medications and commonly used anesthetic drugs during the perioperative period will be reviewed. Finally, recommendations regarding the management of chronic medications during the preoperative period will be provided.Materials and Methods: An online search was conducted from January 2000 through February 2021 with the Medline database through PubMed and Google Scholar using the following search terms/keywords: "chronic medications in the perioperative period", and "chronic medications and anesthetic implications." In addition, we searched for anesthetic side effects associated with the major drug groups.Results and Conclusions: An understanding of the pharmacodynamic effects of most used chronic medications is important to avoid untoward outcomes in the perioperative period. These drug interactions may result in altered efficacy and toxicity of the anesthetic medications administered during surgery. These drug-drug interactions can also affect the morbidity, mortality, recovery time of surgical patients and acute relapse of chronic illnesses which could lead to last minute cancellation of surgical procedures. Part II of this two-part review article focuses on the reported interactions between most commonly taken chronic medications by surgical patients and anesthetic and analgesic drugs, as well as recommendations regarding the handling these chronic medications during the perioperative period.

Impact of chronic medications in the perioperative period: mechanisms of action and adverse drug effects (Part I).

Background: This review article discusses the pharmacology of the most commonly used chronic medications in patients undergoing elective surgical procedures. The mechanism of action and adverse side effects of cardiovascular medications (e.g., beta blockers, alpha-2 agonist, calcium channel blockers, ACE inhibitors, diuretics), lipid-lowering drugs, gastrointestinal medications (H2-blockers, proton pump inhibitors), pulmonary medications (inhaled ß-agonists, anticholinergics,), antibiotics (tetracyclines, clindamycin and macrolide, linezolid), opioids and non-opioids analgesics (NSAIDs, COX-2 inhibitors, acetaminophen), gabapentanoids, erectile dysfunction (ED) drugs, and psychotropic drugs (tricyclic antidepressants [TCAs], monoamine oxidase inhibitors [MAOI], selective serotonin reuptake inhibitors [SSRIs], serotonin norepinephrine reuptake inhibitors [SNRIs], and cannabinol-containing drugs) will be reviewed.Materials and Methods: An online search was conducted from January 2000 through February 2021 with the Medline database through PubMed and Google Scholar using the following search terms/keywords: "chronic medications in the perioperative period", and "chronic medications and anesthetic implications." In addition, we searched for anesthetic side effects associated with the major drug groups.Results and Conclusions: An understanding of the pharmacology and pharmacokinetics of most used chronic medications is important to avoid untoward outcomes in the perioperative period. These drug interactions may result in altered efficacy and toxicity of the anesthetic medications administered during surgery. These drug-drug interactions can also effect the morbidity, mortality, and recovery time of surgical patients. Part I of this two-part review article focuses on the mechanisms of action and adverse side effects of the chronic medications most commonly taken by surgical patients in the preoperative period.

Management strategies for the treatment and prevention of postoperative/postdischarge nausea and vomiting: an updated review.

Postoperative nausea and vomiting (PONV) and postdischarge nausea and vomiting (PDNV) remain common and distressing complications following surgery. The routine use of opioid analgesics for perioperative pain management is a major contributing factor to both PONV and PDNV after surgery. PONV and PDNV can delay discharge from the hospital or surgicenter, delay the return to normal activities of daily living after discharge home, and increase medical costs. The high incidence of PONV and PDNV has persisted despite the introduction of many new antiemetic drugs (and more aggressive use of antiemetic prophylaxis) over the last two decades as a result of growth in minimally invasive ambulatory surgery and the increased emphasis on earlier mobilization and discharge after both minor and major surgical procedures (e.g. enhanced recovery protocols). Pharmacologic management of PONV should be tailored to the patient's risk level using the validated PONV and PDNV risk-scoring systems to encourage cost-effective practices and minimize the potential for adverse side effects due to drug interactions in the perioperative period. A combination of prophylactic antiemetic drugs with different mechanisms of action should be administered to patients with moderate to high risk of developing PONV. In addition to utilizing prophylactic antiemetic drugs, the management of perioperative pain using opioid-sparing multimodal analgesic techniques is critically important for achieving an enhanced recovery after surgery. In conclusion, the utilization of strategies to reduce the baseline risk of PONV (e.g. adequate hydration and the use of nonpharmacologic antiemetic and opioid-sparing analgesic techniques) and implementing multimodal antiemetic and analgesic regimens will reduce the likelihood of patients developing PONV and PDNV after surgery.

Exendin-4 improves behaviorial deficits via GLP-1/GLP-1R signaling following partial hepatectomy.

Recent studies indicate that glucagon-like peptide 1 (GLP-1) receptor (GLP-1R) agonists exhibit neurotrophic and neuroprotective effects. The aim of this study was to explore whether the GLP-1R agonist exendin-4 can alter surgery-induced behavioral deficits and exert neuroprotective effects via the activation of the hippocampal GLP-1/GLP-1R pathway. 120 male Sprague-Dawley rats (aged 18-20 months old) were randomly divided into four groups: control group, exendin-4 group, surgery group, and surgery + exendin-4 group. The animals received either exendin-4 (5 µg/kg/day) or saline intra-peritoneally for 14 days, and then were subjected to partial hepatectomy 24 h after the last injection. Behavioral changes were evaluated with Morris Water Maze and Open field testing on postoperative days 7 and 14. The levels of IL-1ß, NF-κB, Iba-1, Synaptophysin, GLP-1/GLP-1R, GSK-3ß, p-GSK-3ß (Ser9), p-Tau (Ser396), and p-Tau (Ser202/199) in the hippocampus were measured at the same time point. Surgical trauma induced an exacerbated spatial learning and memory impairment, increased the levels of depressive performance, and enhanced hippocampal NF-κB and IL-1ß expression in the aged rats on postoperative day 7. A corresponding decline in GLP-1R was also found following surgical challenge on postoperative day 7. Exendin-4 treatment partly reversed surgery-induced postoperative behavioral impairment, downregulated the levels of NF-κB and IL-1ß, ameliorated tau hyperphosphorylation and enhanced the activity of p-GSK-3ß (Ser9). Together, the downregulation of GLP-1R exacerbated surgery-induced behavior deficits. Exendin-4 treatment attenuated these effects by inhibiting neuroinflammation and tau hyperphosphorylation. These findings suggest that pretreatment with exendin-4 is a potential adjuvant for preventing surgery-induced behavioral deficits.

Treatment of recent onset low back pain with periradicular injections of meloxicam: a randomized, double blind, placebo controlled cross-over study.

BACKGROUND: Low back pain (LBP) is a common and costly illness. This randomized, double-blind, placebo-controlled, cross-over study tested the hypothesis that periradicular injections of meloxicam would reduce LBP and improve physical activity compared to a saline injection at 3 months follow-up. METHODS: After IRB approval, 80 consenting patients suffering LBP of <6 months duration were randomly assigned to the control (C-group, N.=40, receiving 10 mL of saline) or the meloxicam (M-group, N.=40, receiving 10 mg in 10 mL saline). If the pain Numeric Rating Score (NRS) at 24 hours remained >50% of the pretreatment score, the patient was crossed-over to the other group. A successful treatment was NRS<3 at 3 months follow-up. Secondary outcome measures which were assessed included work-absence, physical-assistance, physical-activities limitations and pain-related insomnia. RESULTS: The baseline NRS was 9.3 (95% CI: 8.9-9.7) in the C-group and 9.2 (95% CI: 8.8-9.6) in the M-group. At the 24 hours follow-up after the initial treatment, the mean NRS was 6.3 (95% CI: 5.4-7.2) in the C-group vs. 3.5 (95% CI: 2.6-4.4) in the M-group (P<0.05). The number of cross-over cases was significantly higher in the C-group (N.=31, 77.5% vs. N.=5, 12.5%, P<0.001). At the 3 months follow-up, 66 patients (35+31) were allocated in the M-group and 54 (82%) reported NRS Score <3, while only 14 (9+5) patients remained in the C-group and eight patients had NRS<3. CONCLUSIONS: Periradicular injection of meloxicam is an effective analgesic treatment for acute/subacute LBP. This novel use of meloxicam also leads to an improvement in the level of physical activity at the 3-month follow-up.

Treatment of drug-resistant fibromyalgia symptoms using high-intensity laser therapy: a case-based review.

Fibromyalgia is a chronic musculoskeletal condition characterized by widespread pain in the body and is associated with tender points at the shoulder, back and hip regions. A wide variety of pharmacologic drugs and dietary supplements have been used with limited success in treating the musculoskeletal pain. Early clinical studies with low level laser therapy (LLLT) alone or in combination with drugs commonly used to treat fibromyalgia suggested that LLLT may be effective in reducing musculoskeletal pain and stiffness, as well as the number of tender locations. However, a sham-controlled study reported that LLLT was not significantly better than the sham treatment and kinesiotape. Preliminary studies with high-intensity laser therapy (HILT) suggest that it may be more effective than LLLT for treating chronic pain syndromes. Therefore, we evaluated low (1 W), intermediate (42 W) and high level (75 W) HILT in a woman with long-standing fibromyalgia syndrome which was resistant to both standard pharmacotherapy and treatment in an interdisciplinary pain management program. The patient received a series of treatments with a HILT device (Phoenix Thera-lase) at a wavelength of 1275 nm administered at both the paraspinous region and tender points in the shoulder and hip regions. Although the 1 W treatment produced minimal symptom relief, both the 42 and the 75 W treatments produced a dramatic reduction in her overall pain, improved quality of sleep, and increased her level of physical activity for 4-10 days after these treatment sessions. This case illustrates the potential beneficial effects of using higher power levels of HILT for patients with fibromyalgia syndrome who have failed to respond to conventional interdisciplinary treatment regimens.

Perioperative Care of Elderly Surgical Outpatients.

The ambulatory setting offers potential advantages for elderly patients undergoing elective surgery due to the advancement in both surgical and anesthetic techniques resulting in quicker recovery times, fewer complications, higher patient satisfaction, and reduced costs of care. This review article aims to provide a practical guide to anesthetic management of elderly outpatients. Important considerations in the preoperative evaluation of elderly outpatients with co-existing diseases, as well as the advantages and disadvantages of different anesthetic techniques on a procedural-specific basis, and recommendations regarding the management of common postoperative complications (e.g., pain, postoperative nausea and vomiting [PONV], delirium and cognitive dysfunction, and gastrointestinal dysfunction) are discussed. The role of anesthesiologists as perioperative physicians is important for optimizing surgical outcomes for elderly patients undergoing ambulatory surgery. The implementation of high-quality, evidence-based perioperative care programs for the elderly on an ambulatory basis has assumed increased importance. Optimal management of perioperative pain using opioid-sparing multimodal analgesic techniques and preventing PONV using prophylactic antiemetics are key elements for achieving enhanced recovery after surgery.