Randomized Clinical Trial of Moderate Versus Deep Neuromuscular Block for Low-Pressure Pneumoperitoneum During Laparoscopic Cholecystectomy
Koo. World J Surg; Published first on line 12th July 2016 doi:10.1007/s00268-016-3633-8
- In patients undergoing elective laparoscopic cholecystectomy, does deep neuromuscular blockade permit the use of low-pressure pneumoperitoneum?
- Single-centre, randomised-controlled trial
- Computer generated randomisation using sealed, opaque envelopes
- Surgeon and staff assessing post-op outcomes were blinded
- Sample size calculation: α-error: 0.05, power of 80% to detect a ≥30% reduction in the rate of increasing intraabdominal inflation pressure. => 32 patients need in each group.
- Single university hospital in Seoul
- From September 2013 to April 2014
- Inclusion: Age 18-69, ASA I-II, scheduled to undergo elective cholecystectomy
- Exclusion: History of neuromuscular, renal or hepatic disease, BMI <18.5 or >30, previous abdominal surgery, acute cholecystitis and treatment with medications that are known to interfere with neuromuscular function
- 96 patients assessed, 70 randomised, only 32 received intervention in each group. None lost to follow up. Per-protocol analysis performed.
- Deep neuromuscular blockade
- Rocuronium boluses to maintain Post-tetanic count of 1 or 2.
- Reversed with Sugammadex (4mg/kg) at the end
- Moderate neuromuscular blockade
- Rocuronium boluses to maintain Train-of-Four count of 1 or 2.
- Reversed with Neostigmine/Glycopyrrolate at the end
Management common to both:
- Midazolam pre-med (0.02mg/kg).
- Propofol and Remifentanil TCI used for induction and maintenance, with BIS monitoring
- Accelerometric monitoring, calibrated before paralysis
- Rocuronium (0.6mg/kg) on induction, 5-10mg boluses afterwards
- Initial inflation pressure at 8mmHg, increased to 12mmHg on surgeon’s request
- Primary outcome: Rate of increasing intra-abdominal pressure following request by surgeon due to inadequate surgical conditions
- Deep blockade 12.5% vs. Moderate blockade 34.4%
- Chi-squared test: p=0.039
- Fisher’s exact test: p=0.0746!
- Absolute Risk Reduction: 21.9%
- NNT: 5
- Fragility Index zero
- Secondary outcome:
- Surgical condition were rated as good or excellent more often in the deep blockade group
- Operation time was significantly reduced in the deep blockade group
- Observed intra-operative movements occurred less frequently in the deep blockade group
- Post-operative complaints of: nausea and vomiting, pain, dry mouth and shoulder tip pain were less frequent in the deep blockade group, but only statistically significantly so at 24 hours and not 30 minutes
- The use of deep neuromuscular blockade with close monitoring and full and reliable reversal with sugammadex, permits the use of lower inflation pressures during laparoscopic cholecystectomy
- Effective randomisation with similar baseline characteristics in both groups
- Blinded surgeons and staff assessing post-op outcomes
- Interesting results with regards to shoulder tip pain, PONV and dry mouth, but the study is not sufficiently powered to assess these
- Careful monitoring of depth of neuromuscular blockade
- The lower pressure (8mmHg) pneumoperitoneum is significantly less than in some of the cited studies looking at this topic. However, the exclusion of obese (BMI>30) patients may partly explain why this pressure still provided adequate conditions in most cases
- Patients in the moderate blockade group were reversed from a relatively deep level of blockade(TOF count of 1 or 2), which is deeper than normally recommended(TOF count >2). This could have affected the time to TOF ratio of 0.9.
- It is unclear if the “Postoperative pain” assessment included shoulder tip pain or not.
- Internal validity may be reduced:
- Per protocol analysis. 6 patients excluded from analysis.
- If Fisher’s exact test is applied to the primary outcome (rather than Chi Squared), the result is p=0.075, making it statistically non-significant.
- Only 96 patients assessed for eligibility in 8 months, in a 1782 bed university hospital. Could this produce selection bias?
- External validity may be reduced:
- Deep neuromuscular blockade requires close monitoring using quantitative devices, which aren’t universally available
- Adequate reversal before extubation to avoid adverse effects requires sugammadex, which is still relatively expensive limiting its availability
- Acute cholecystitis – “hot lap choles” are becoming more common and it is a patient population who could potentially benefit more from lower pressure pneumoperitoneum, with systemic physiological derangement potentially already present preoperatively
- “History of renal or hepatic disease” – very vague, and covering a very large proportion of patients
- Exclusion of obese patients – a growing proportion of our patient population, especially for this operation
The Bottom Line
- A well conducted, small RCT with interesting results, that are probably valid but not widely generalizable. A larger trial with appropriate inclusion criteria and statistical tests is needed to confirm this hypothesis.
- I will consider the use of deep neuromuscular blockade and sugammadex reversal in patients who may be particularly sensitive to pneumoperitoneum to allow lower inflation pressures.
- [article] Randomized Clinical Trial of Moderate Versus Deep Neuromuscular Block for Low-Pressure Pneumoperitoneum During Laparoscopic Cholecystectomy
- [further reading] Sugammadex by LITFL
- [further reading] Monitoring of Neuromuscular Block by BJA Education