Evaluation of Malignant Hyperthermia Features in Patients with Pathogenic or Likely Pathogenic RYR1 Variants Disclosed through a Population Genomic Screening Program.

BACKGROUND: Malignant hyperthermia (MH) susceptibility is a heritable musculoskeletal disorder that can present as a potentially fatal hypermetabolic response to triggering anesthesia agents. Genomic screening for variants in MH-associated genes RYR1 and CACNA1S provides an opportunity to prevent morbidity and mortality. There are limited outcomes data from disclosing variants in RYR1, the most common MH susceptibility gene, in unselected populations. The authors sought to identify the rate of MH features or fulminant episodes after triggering agent exposure in an unselected population undergoing genomic screening including actionable RYR1 variants. METHODS: The MyCode Community Health Initiative by Geisinger (USA) is an electronic health record-linked biobank that discloses pathogenic and likely pathogenic variants in clinically actionable genes to patient-participants. Available electronic anesthesia and ambulatory records for participants with actionable RYR1 results returned through December 2020 were evaluated for pertinent findings via double-coded chart reviews and reconciliation. Descriptive statistics for observed phenotypes were calculated. RESULTS: One hundred fifty-two participants had an actionable RYR1 variant disclosed during the study period. None had previous documented genetic testing for MH susceptibility; one had previous contracture testing diagnosing MH susceptibility. Sixty-eight participants (44.7%) had anesthesia records documenting triggering agent exposure during at least one procedure. None received dantrolene treatment or had documented muscle rigidity, myoglobinuria, hyperkalemia, elevated creatine kinase, severe myalgia, or tea-colored urine. Of 120 possibly MH-related findings (postoperative intensive care unit admissions, hyperthermia, arterial blood gas evaluation, hypercapnia, or tachycardia), 112 (93.3%) were deemed unlikely to be MH events; 8 (6.7%) had insufficient records to determine etiology. CONCLUSIONS: Results demonstrate a low frequency of classic intraanesthetic hypermetabolic phenotypes in an unselected population with actionable RYR1 variants. Further research on the actionability of screening for MH susceptibility in unselected populations, including economic impact, predictors of MH episodes, and expanded clinical phenotypes, is necessary.

A prospective randomized trial of lidocaine 30 mg versus 45 mg for epidural test dose for intrathecal injection in the obstetric population.

BACKGROUND: The epidural test dose, used to identify unintended intrathecal placement, should reliably produce a spinal block without posing a threat to the patient. Most anesthesiologists administer a dose of local anesthetic, commonly lidocaine 45 mg. Pregnant patients are more sensitive to local anesthetics; high and total spinal anesthesia have been reported in the pregnant population with this dose. We hypothesized that lidocaine 30 mg was as effective as lidocaine 45 mg in creating rapid objective evidence of a sensory or motor block. METHODS: In this prospective, randomized, double-blind trial, patients scheduled for cesarean delivery were assigned to 1 of 4 groups: lidocaine 30 mg in the spinal or epidural space, or lidocaine 45 mg by the same routes. A blinded observer assessed the degree of sensory and motor block. The ability to identify intrathecal injection of each dose was compared. Sensory block above T6 dermatome and hypotension were recorded as side effects. RESULTS: Intrathecal administration of lidocaine 30 mg produced rapid subjective and objective signs of neuroblockade within 3 minutes (100%, 95% confidence interval CI, 85%-100% for each). Lidocaine 45 mg produced similar results. All patients in both groups described their legs as warm or heavy after 3 minutes and had a motor block by 5 minutes. On the basis of an intrathecal catheter rate of 1:380, the observed negative predictive value for intrathecal placement if the patient described no sensory changes at 3 minutes was 100% (95% CI, 99.95%-100%) for 30 mg and 100% (95% CI, 99.93%-100%) for 45 mg. We did not identify a decrease in the rate of side effects with the lower dose. CONCLUSIONS: Our results suggest that there is unlikely to be a large difference in the ability of these doses to detect unintentional intrathecal catheter placement. While the negative predictive value for intrathecal injection is very high for both doses, the 95% CI for the sensitivity of either dose is too wide to demonstrate clinical safety to identify all intrathecal catheters. A much larger study is warranted to assess whether there is a lower sensitivity with the 30-mg dose, or a propensity toward high cephalad motor block levels with the 45-mg dose.

Small dose bupivacaine-fentanyl spinal analgesia combined with morphine for labor.

UNLABELLED: We investigated the duration of labor analgesia produced by a small dose of spinal bupivacaine/fentanyl alone or in combination with a small dose of morphine. Sixty parturients were enrolled in this placebo-controlled, double-blinded, randomized trial. All women received a spinal injection of 12.5 micro g of fentanyl with 2 mg of bupivacaine. The morphine group (MBF) also received 125 micro g of morphine; the placebo group (BF) received saline. Pain scores were <3 of 10 within 10 min of injection. The median duration of analgesia was similar between groups (89 min versus 84 min; P = not significant), and only 20% of the MBF group experienced prolonged analgesia. During subsequent epidural analgesia, the MBF group had a significantly lesser rate of breakthrough pain (0.15 +/- 0.14 episodes per hour versus 0.26 +/- 0.18 episodes per hour; P = 0.02). Also, during the first 24 h postpartum, the MBF group required significantly fewer medications (3.3 +/- 3.7 doses versus 4.7 +/- 3.5 doses; P = 0.04). Intrathecal injection of this small dose of bupivacaine/fentanyl produced a rapid onset of labor analgesia; the addition of a small dose of morphine did not significantly prolong analgesia, but it improved subsequent pain relief, as measured by the rate of breakthrough pain and postpartum medication requirements. This may provide a clinically useful means of improving intra- and postpartum pain relief. IMPLICATIONS: A small dose of intrathecal fentanyl 12.5 micro g and bupivacaine 2 mg produces effective labor analgesia lasting for approximately 85 min. The addition of a small 125- micro g dose of morphine improves pain control during subsequent epidural analgesia and reduces the requirements for postpartum pain medications.