Cannabis Use and Inhalational Anesthesia Administration in Older Adults: A Propensity Matched Retrospective Cohort Study.

BACKGROUND: Cannabis use is associated with higher intravenous anesthetic administration. Similar data regarding inhalational anesthetics are limited. With rising cannabis use prevalence, understanding any potential relationship with inhalational anesthetic dosing is crucial. We compared average intraoperative isoflurane/sevoflurane minimum alveolar concentration equivalents between older adults with and without cannabis use. METHODS: The electronic health records of 22,476 surgical patients ≥65 years old at the University of Florida Health System between 2018-2020 were reviewed. The primary exposure was cannabis use within 60 days of surgery, determined via i) a previously published natural language processing algorithm applied to unstructured notes and ii) structured data, including International Classification of Disease codes for cannabis use disorders and poisoning by cannabis, laboratory cannabinoids screening results, and RxNorm codes. The primary outcome was the intraoperative time-weighted average of isoflurane/sevoflurane minimum alveolar concentration equivalents at one-minute resolution. No a priori minimally clinically important difference was established. Patients demonstrating cannabis use were matched 4:1 to non-cannabis use controls using a propensity score. RESULTS: Among 5,118 meeting inclusion criteria, 1,340 patients (268 cannabis users and 1,072 nonusers) remained after propensity score matching. The median and interquartile range (IQR) age was 69 (67, 73) years; 872 (65.0%) were male, and 1,143 (85.3%) were non-Hispanic White. The median (IQR) anesthesia duration was 175 (118, 268) minutes. After matching, all baseline characteristics were well-balanced by exposure. Cannabis users had statistically significantly higher average minimum alveolar concentrations than nonusers [mean±SD: 0.58±0.23 versus 0.54±0.22, respectively; mean difference=0.04; 95% confidence limits, 0.01 to 0.06; p=0.020]. CONCLUSION: Cannabis use was associated with administering statistically significantly higher inhalational anesthetic minimum alveolar concentration equivalents in older adults, but the clinical significance of this difference is unclear. These data do not support the hypothesis that cannabis users require clinically meaningfully higher inhalational anesthetics doses.

Neurobehavioral Abnormalities in Offspring of Young Adult Male Rats With a History of Traumatic Brain Injury.

Children of parents with traumatic brain injury (TBI) are more likely to develop psychiatric disorders. This association is usually attributed to TBI-induced changes in parents' personality and families' social environment. We tested the hypothesis that offspring of young adult male rats with TBI develop neurodevelopmental abnormalities in the absence of direct social contact with sires. Male Sprague-Dawley rats (F0 generation) in the TBI group underwent moderate TBI via a midline fluid percussion injury that involved craniectomy under sevoflurane (SEVO) anesthesia for 40 min on post-natal Day 60 (P60), while F0 rats in the control group were placed in a new cage, one per cage, for the equivalent time duration. A subset of F0 rats was sacrificed on P66 to assess acute changes in hypothalamic-pituitary-adrenal (HPA) axis and inflammation markers. The remaining F0 males were mated with naive females on P90 to generate offspring (F1 generation). The F0 males and F1 males and females were sequentially evaluated in the elevated plus maze, for pre-pulse inhibition of acoustic startle, in the Morris water maze, and for resting and stress levels of serum corticosterone starting on ∼P105 (F0) and ∼P60 (F1), followed by tissue collection for further analyses. Acutely, the F0 TBI males had messenger RNA (mRNA) transcripts altered to support an increased hypothalamic and hippocampal Na+-K+-Cl- (Slc12a2) Cl- importer / K+-2Cl- (Slc12a5) Cl- exporter ratio and decreased hippocampal glucocorticoid receptors (Nr3c1), as well as increased serum levels of corticosterone, interleukin-1ß (IL-1ß), and biomarkers of activated hippocampal microglia and astrocytes. Long-term, F0 TBI rats exhibited increased corticosterone concentrations at rest and under stress, anxiety-like behavior, impaired sensory-motor gating, and impaired spatial memory. These abnormalities were underpinned by reduced mRNA levels of hypothalamic and hippocampal mineralocorticoid receptors (Nr3c2), hippocampal Nr3c1, and hypothalamic brain-derived neurotrophic factor (Bdnf), as well as elevated serum levels of IL-1ß, and biomarkers of activated hippocampal microglia and astrocytes. F1 male offspring of TBI sires exhibited abnormalities in all behavioral tests, while their F1 female counterparts had abnormal pre-pulse inhibition responses only. F1 male offspring of TBI sires also had reduced mRNA levels of hippocampal Nr3c1 and Nr3c2, as well as hypothalamic and hippocampal Bdnf, whereas increases in inflammatory markers were more profound in F1 females. These findings suggest that offspring of sires with a history of a moderate TBI that involved craniectomy under SEVO anesthesia for 40 min, develop sex-dependent neurobehavioral abnormalities in the absence of direct social interaction between the sire and the offspring.

Dosing Cefazolin for Surgical Site Infection Prophylaxis in Adolescent Idiopathic Scoliosis Surgery: Intermittent Bolus or Continuous Infusion?-A Pilot Study.

Background: Cefazolin may minimize the risk of surgical site infection (SSI) following posterior spinal fusion (PSF) for adolescent idiopathic scoliosis (AIS). Cefazolin dosing recommendations vary and there is limited evidence for achieved tissue concentrations. Methods: We performed a randomized, controlled, prospective pharmacokinetic pilot study of 12 patients given cefazolin by either intermittent bolus (30 mg/kg every 3 h) or continuous infusion (30 mg/kg bolus followed by 10/mg/kg per hour) during PSF for AIS. Results: Patients were well matched for demographic and perioperative variables. While total drug exposure, measured as area-under-the-curve (AUC), was similar in plasma for bolus and infusion dosing, infusion dosing achieved greater cefazolin exposure in subcutaneous and muscle tissue. Using the pharmacodynamic metric of time spent above minimal inhibitory concentration (MIC), both bolus and infusion dosing performed well. However, when targeting a bactericidal concentration of 32 µg/mL, patients in the bolus group spent a median of 1/5 and 1/3 of the typical 6 h operative time below target in subcutaneous and muscle tissue, respectively. Conclusions: We conclude that intraoperative determination of cefazolin tissue concentrations is feasible and both bolus and infusion dosing of cefazolin achieve concentrations in excess of typical MICs. Infusion dosing appears to more consistently achieve bactericidal concentrations in subcutaneous and muscle tissues.

Cannabis use and acute postoperative pain outcomes in older adults: a propensity matched retrospective cohort study.

INTRODUCTION: Cannabis use is increasing among older adults, but its impact on postoperative pain outcomes remains unclear in this population. We examined the association between cannabis use and postoperative pain levels and opioid doses within 24 hours of surgery. METHODS: We conducted a propensity score-matched retrospective cohort study using electronic health records data of 22 476 older surgical patients with at least 24-hour hospital stays at University of Florida Health between 2018 and 2020. Of the original cohort, 2577 patients were eligible for propensity-score matching (1:3 cannabis user: non-user). Cannabis use status was determined via natural language processing of clinical notes within 60 days of surgery and structured data. The primary outcomes were average Defense and Veterans Pain Rating Scale (DVPRS) score and total oral morphine equivalents (OME) within 24 hours of surgery. RESULTS: 504 patients were included (126 cannabis users and 378 non-users). The median (IQR) age was 69 (65-72) years; 295 (58.53%) were male, and 442 (87.70%) were non-Hispanic white. Baseline characteristics were well balanced. Cannabis users had significantly higher average DVPRS scores (median (IQR): 4.68 (2.71-5.96) vs 3.88 (2.33, 5.17); difference=0.80; 95% confidence limit (CL), 0.19 to 1.36; p=0.01) and total OME (median (IQR): 42.50 (15.00-60.00) mg vs 30.00 (7.50-60.00) mg; difference=12.5 mg; 95% CL, 3.80 mg to 21.20 mg; p=0.02) than non-users within 24 hours of surgery. DISCUSSION: This study showed that cannabis use in older adults was associated with increased postoperative pain levels and opioid doses.