Daily Anesthesiology Research Analysis
Three randomized clinical trials inform perioperative anesthesia practice: intrathecal hydromorphone was noninferior to morphine for post-cesarean analgesia; prophylactic intravenous calcium gluconate during intrapartum cesarean under spinal anesthesia reduced postpartum blood loss and additional uterotonic use; and intercostal cryoanalgesia did not improve acute pain after VATS and was associated with higher cough pain at 1 month.
Summary
Three randomized clinical trials inform perioperative anesthesia practice: intrathecal hydromorphone was noninferior to morphine for post-cesarean analgesia; prophylactic intravenous calcium gluconate during intrapartum cesarean under spinal anesthesia reduced postpartum blood loss and additional uterotonic use; and intercostal cryoanalgesia did not improve acute pain after VATS and was associated with higher cough pain at 1 month.
Research Themes
- Obstetric anesthesia: optimizing neuraxial opioid strategies and hemorrhage mitigation
- Perioperative multimodal analgesia: evaluating novel regional/adjunct techniques
- Practice-changing trials and the value of negative RCTs
Selected Articles
1. Intrathecal Hydromorphone Versus Intrathecal Morphine for Postcesarean Delivery Analgesia: A Randomized Noninferiority Trial.
In 126 elective cesarean patients, intrathecal hydromorphone 75 µg was noninferior to morphine 150 µg for 24-hour pain (mean difference -0.46; 95% CI -1.0 to 0.1). Opioid consumption, quality of recovery (ObsQoR-11), time to first opioid, and pruritus/nausea interventions were similar, with no neonatal differences.
Impact: Addresses opioid selection in cesarean spinal anesthesia using a rigorous noninferiority RCT, supporting hydromorphone as a viable alternative during shortages or intolerance to morphine.
Clinical Implications: Intrathecal hydromorphone 75 µg can substitute for morphine 150 µg for post-cesarean analgesia without compromising pain control or recovery metrics, informing formularies and protocols during drug shortages or patient-specific intolerance.
Key Findings
- Hydromorphone 75 µg was noninferior to morphine 150 µg for 24-hour mean NRS pain after cesarean (difference -0.46; 95% CI -1.0 to 0.1).
- No significant differences in 24-hour oral morphine equivalents, ObsQoR-11, time to first opioid, or pruritus/nausea interventions.
- Neonatal outcomes (Apgar scores) were comparable between groups.
Methodological Strengths
- Randomized, blinded noninferiority design with prespecified margin.
- Use of established ED90 dosing and multiple clinically relevant secondary outcomes.
Limitations
- Primary pain outcome was recall-based at 24 hours, introducing potential recall bias.
- Moderate sample size and elective cesarean population may limit generalizability to higher-risk patients.
Future Directions: Multicenter trials to confirm findings across diverse populations, standardized dosing/monitoring protocols, and evaluation of maternal side effects, breastfeeding outcomes, and rare adverse events.
BACKGROUND: Spinal anesthesia with intrathecal morphine is often the preferred anesthetic modality for elective cesarean delivery. Side effects and drug shortages, however, prompted researchers to look into intrathecal hydromorphone as an alternative. These studies established the effective analgesic dose for 90% of patients (ED90) for both opioids for postcesarean analgesia, yet failed to demonstrate the superiority of morphine over hydromorphone. Nonetheless, the noninferiority of hydromorphone has yet to be determined. METHODS: In this noninferiority randomized blinded clinical trial, 126 patients undergoing elective cesarean delivery under spinal anesthesia received either morphine 150 µg or hydromorphone 75 µg (ED90). The primary outcome was the between-group difference of the mean Numeric Rating Scale (NRS) pain score (0-10) for the first 24 hours after cesarean delivery, with a preestablished threshold for noninferiority of 1. This 24-hour NRS pain score was defined as a single number obtained at the 24 hours postcesarean delivery interview, based on participant's recall of their overall pain experience during this period. Secondary outcomes included differences in NRS pain scores every 6 hours, cumulative 24 hour opioid consumption, time-to-first opioid request, quality of recovery as measured by the Obstetric Quality of Recovery Score-11 (ObsQoR-11), frequency of interventions for side effects, and Apgar scores.
2. Effect of prophylactic intravenous calcium gluconate on uterine atony during intrapartum cesarean delivery with spinal anesthesia: a placebo controlled, randomized clinical trial.
Among 367 intrapartum cesarean patients, prophylactic calcium did not improve obstetrician-rated uterine tone change from baseline, but reduced postpartum blood loss by 55.6 mL (95% CI 24.3–86.8; P=0.001) and halved additional uterotonic use (21.7% vs 42.39%; RR 0.51; 95% CI 0.37–0.71). Transfusion and vasopressor needs were similar.
Impact: A large, blinded RCT in a high-risk obstetric setting suggests a simple, low-cost intervention may reduce blood loss and uterotonic needs despite a negative primary tone outcome.
Clinical Implications: For intrapartum cesarean under spinal anesthesia, 1 g IV calcium gluconate after cord clamping may be considered to reduce blood loss and additional uterotonic administration. Implementation should weigh subjective tone assessment and unchanged transfusion outcomes.
Key Findings
- No significant improvement in obstetrician-rated uterine tone change from baseline (P=0.11).
- Lower postpartum blood loss with calcium (526.0 ± 155.2 vs 581.5 ± 148.9 mL; mean difference 55.6 mL; 95% CI 24.3–86.8; P=0.001).
- Reduced need for additional uterotonics (21.7% vs 42.39%; RR 0.51; 95% CI 0.37–0.71; P=0.001), with similar transfusion and vasopressor requirements.
Methodological Strengths
- Prospective, randomized, placebo-controlled, blinded design with adequate sample size.
- Prospectively registered trial with clinically meaningful secondary endpoints.
Limitations
- Primary outcome (uterine tone score) was subjective and operator-assessed.
- Single-country setting; transfusion outcomes did not differ despite reduced blood loss.
Future Directions: Multicenter trials to validate findings, explore dosing/timing, and assess high-risk atony populations with standardized, objective uterine contractility metrics and clinically hard endpoints.
BACKGROUND: Nearly two-thirds of postpartum hemorrhage is due to uterine atony. Calcium ions play a vital role in myometrial contraction and may improve uterine tone. However, studies utilizing calcium to prevent uterine atony are limited, and have yielded conflicting findings. We designed this study to evaluate the effect of prophylactic intravenous calcium on uterine tone during intrapartum cesarean delivery with spinal anesthesia. METHOD: This prospective, randomized, placebo-controlled, two-arm blinded trial was performed in patients undergoing intrapartum cesarean delivery with spinal anesthesia. Patients were randomized to receive intravenous calcium gluconate 1 g (93 mg elemental calcium) or placebo (normal saline) over 10 minutes after umbilical cord clamping. The primary outcome measure was uterine tone, assessed five times by the obstetrician using an 11-point verbal numeric rating score (0 = completely atonic; 10 = fully contracted). Secondary outcomes were postpartum blood loss, additional uterotonic administration, and blood product transfusion.
3. Intercostal cryoanalgesia for acute pain after video-assisted thoracic surgery lung resection: A randomized controlled preliminary trial.
Intercostal cryoanalgesia added to standard multimodal analgesia with paravertebral block did not reduce 24-hour cough pain after VATS (4.7 ± 2.7 vs 4.8 ± 2.9; P=0.78), nor improve acute recovery metrics up to 7 days. Cough pain was higher at 1 month in the cryo group (4.7 ± 2.4 vs 3.4 ± 2.0; P=0.036), with no differences at 3 or 6 months.
Impact: A double-blind RCT provides high-quality negative evidence against routine intercostal cryoanalgesia as an adjunct after VATS, potentially averting adoption of an ineffective (and possibly harmful at 1 month) intervention.
Clinical Implications: Do not routinely add intercostal cryoanalgesia to single-shot paravertebral-based multimodal analgesia after VATS lung resection; focus on optimizing regional techniques and systemic multimodal strategies with proven benefit.
Key Findings
- No difference in 24-hour cough pain between cryoanalgesia and control (4.7 ± 2.7 vs 4.8 ± 2.9; P=0.78).
- No improvements in acute recovery measures (opioid consumption, side effects, QoR) up to 7 days; sensory loss and DN4 neuropathic scores were comparable.
- Higher cough pain at 1 month in cryo group (4.7 ± 2.4 vs 3.4 ± 2.0; P=0.036), with no differences at 3 and 6 months.
Methodological Strengths
- Randomized, double-blind, controlled design with active multimodal analgesia in both groups.
- Longitudinal assessment up to 6 months with validated pain and neuropathic measures.
Limitations
- Preliminary sample size (n=80) limits power for rare adverse events and subgroup analyses.
- Single-procedure context (VATS lobectomy) may limit generalizability to other thoracic procedures.
Future Directions: Further trials should evaluate different cryo parameters, patient selection, and compare against continuous regional techniques; investigate mechanisms underlying increased 1-month cough pain.
OBJECTIVE: Video-assisted thoracoscopic surgery (VATS) is associated with significant postoperative pain. Multimodal analgesia, including single-shot paravertebral blocks, is widely used but provides limited analgesic duration. Intercostal cryoanalgesia, which offers prolonged pain relief, presents a promising adjunctive option. This study aimed to assess the analgesic benefit of intercostal cryoanalgesia in VATS lung cancer surgery. The primary outcome was thoracic pain during cough 24 hours postsurgery, measured via a verbal numerical rating scale. METHODS: In a randomized, double-blind, controlled trial, 80 patients undergoing VATS lobectomy for lung cancer were assigned to either a control group receiving standard multimodal analgesia with single-shot paravertebral blocks or a cryoanalgesia group receiving additional transpleural intercostal cryoanalgesia (Cryoprobe; Erbe). Thoracic pain at rest and during cough was evaluated at multiple time points up to 6 months postoperatively. Secondary outcomes included quality of recovery, oral morphine equivalents consumption, side effects, thoracic sensory loss (Von Frey filament), and neuropathic pain (Douleur neuropathique 4 score).