Journal Club 2012-2013

Faculty: I Rampil, U Landman
Updated: 04-26-13

Drs. Kim & Joseph
Curry Club
Reading the Medical Literature
Dr. Kim gave a concise review of the User's Guide article that asks the question: are the results of the study valid? We now know the distinction between primary and secondary validity criteria for medical articles. The framework is important to know if the study was valid and what were the results as well as will the results help me in caring for my patients?
We saw that it is important to look at sample size. Current practice requires a power analysis before the study is done. This will tell us if there are enough patients in the study to answer the study's question. We also discussed confidence intervals. The term "surrogate endpoint" was discussed. A surrogate endpoint is often used when it may be too difficult or time-consuming to measure the clinically important endpoint. The validity of the surrogate endpoint must be considered when assessing a medical article.

The topcial article on postoperative QT Interval prolongation in patients undergoing Noncardiac Surgery under General anesthesia was discussed by Dr. Joseph. The hypothesis of the study was that a patient undergoing major surgery under GA will be at risk for QT prolongation. We discussed that corrected QT interval is what the FDA is using to issue warnings on medications. In the study, at the end of surgery, (within 30 minutes arrival to PACU), 80% of patients had significant prolongation of the QT interval. The average increase was 23±26 ms. The confidence interval crosses zero, so there was a very wide dispersion in the results. We discussed the validity of the QT interval as a surrogate. It is not a perfect surrogate. In fact, it is not a perfect predictor. Patients can have MI or VFIB without QT prolongation. It was also noted that torsade is a rare occurance which the FDA is advising about.
Users' guides to the medical literature. I. How to get started. The Evidence-Based Medicine Working Group. Oxman AD, Sackett DL, Guyatt GH. JAMA. 1993 Nov 3;270(17):2093-5. [PubMed]

Users' guides to the medical literature. II. How to use an article about therapy or prevention. A. Are the results of the study valid? Evidence-Based Medicine Working Group. Guyatt GH, Sackett DL, Cook DJ. JAMA. 1993 Dec 1;270(21):2598-601.[PubMed]

Users' guides to the medical literature. II. How to use an article about therapy or prevention. B. What were the results and will they help me in caring for my patients? Evidence-Based Medicine Working Group. Guyatt GH, Sackett DL, Cook DJ. JAMA. 1994 Jan 5;271(1):59-63. [PubMed]

Postoperative QT Interval Prolongation in Patients Undergoing Noncardiac Surgery under General Anesthesia. Nagele P, Pal S, Brown F, Blood J, Miller JP, Johnston J. Anesthesiology. 2012 Aug;117(2):321-328. [PubMed]
Drs. Q (Simon) Guo, and Usman Shah
HSC Galleria
Analysis of Meta-Analysis
Dr. Guo gave us a concise review of the Rawlinson, et al. article on PONV. This review of randomized control trials found that epidural anesthesia failed to reduce length of stay or the incidence of PONV when compared to controls. Paracetamol did not reduce incidence of PONV. NSAID reduced postop opiod consumption and PONV. Cumulative dose of morphine was used as a surrogate since it is easier to measure than pain. A more important fact to consider would be morphine's association with respiratory depression rather than how much of it was used. Dexamathasone and 5-HT 3 antagonists reduced PONV incidence in comparison to controls.
Dr. Shah gave a complete review of the Delaney article about meta-analyses. We discussed the reasons that we see so many meta-analyses recently. A possible reason may be that considering the  time and money needed to get a study published, a meta-analysis may be easier to do because no original information is needed. This article did have a good assessment that is easy enough for us to use vs a statistic comparison. The data collection form for the quality of a meta-analyses asks 9 questions having yes/no/maybe answers to help us rate the quality of the overview. Questions to look at:
1. Were the search methods used to find the evidence on the primary question stated?
2. Was the search for evidence reasonably comprehensive?
3. Were the criteria used for deciding which studies to include in the overview reported?
4. Was bias in the selection of studies avoided.
5. Were the criteria used for assessing the validity of the included studies reported ?
6. Was the Validity of all the studies referred to in the text assesses using appropriate criteria?
7. Were the methods used to combine the findings of the relevant reported?
8. Were the findings of the relevant studies combined appropriately relative to the primary question of the overview?
9. Were the conclusions made by the author supported by the data and or analysis reported in the overview?

We should all keep these in mind next time we read a meta-analysis.

Mechanisms of reducing postoperative pain, nausea and vomiting: a systematic review of current techniques. Rawlinson A, Mohammed A, Beatty J, Bell R, Miller M.. Expert Rev Anticancer Ther. 2012 Apr;12(4):429-37. [PubMed]

A systematic evaluation of the quality of meta-analyses in the critical care literature. Delaney A, Bagshaw SM, Ferland A, Manns B, Laupland KB, Doig CJ. Crit Care. 2005 Oct 5;9(5):R575-82.[PubMed]
Drs. Vuong and Mark Kim
6 pm

Curry Club
Prevention of Bleeding. Residual Neuromuscular Block.
Dr. Vuong gave us a concise review of the fibrinogen article. This was a prospective, placebo-controlled, double blind study. This  study hypothesized that in bleeding patients undergoing AVR, administration of fibrinogen concentrate can safely reduce need for blood transfusion. Patients were randomized to fibrinogen concentrate or placebo prior to surgery. Patients were medicated if significant bleeding occurred. Study medication (fibrinogen 1g vs saline) was prepared by the  pharmacist and  delivered in identical containers to the clinician. Transfusion of allogenic blood was reduced by 85% in treatment group. Total avoidance of transfusion in 13/29 patients (vs. all pts transfused in ctrl group). Re-operation in 4 patients in fibrinogen group vs. control. There were advantages of fibrinogen administration: immediately availability, no need for blood group matching and low administration volume. There were limitations to the study: It was not designed to detect differences in morbidity/mortality vs placebo, Use of 5 min bleeding mass objective - but not a standard of care, and patients with coagulopathy or anticoagulation therapy were excluded. (These patients would have a higher EBL). There was also a limited sample size (29 in the fibrinogen group and 32 in the placebo group) from a single center. The study got promising positive results which will enable a company to fund them for a larger study.
Dr. M. Kim  gave a complete review of the article on residual paralysis. This was a prospective, nonrandomized, open labeled and observational study. We discussed the implications of residual paralysis (hypoxia, hypercarbia, reintubation, delayed discharge from the PACU, greater investigative studies for the patient). Since 2000, the threshold of residual paralysis has been a TOF ratio of 0.9 (previously 0.7) at the adductor pollicis. This study found that after a single does of intermediate muscle relaxant and no reversal, residual paralysis was common, even more than 2 hours after the muscle relaxant was given. This study used an acceleromyographic method to measure quantitatively the TOF ratio. The clinical test such as the tongue depressor test was a poor surrogate  test because the test is done after the patient is extubated. Overall, it appears that our current clinical practice is acceptable and we do not have to run out and buy accelerometers! This article also had some nice scatter graphs of the TOF ratios in all patients, rocuronium, atracurium, and vecuronium.
Effects of fibrinogen concentrate as first-line therapy during major aortic replacement surgery: a randomized, placebo-controlled trial. Rahe-Meyer N, Solomon C, Hanke A, Schmidt DS, Knoerzer D, Hochleitner G, Sørensen B, Hagl C, Pichlmaier M. Anesthesiology. 2013 Jan;118(1):40-50. [PubMed]
Residual paralysis in the PACU after a single intubating dose of nondepolarizing muscle relaxant with an intermediate duration of action. Debaene B, Plaud B, Dilly MP, Donati F. Anesthesiology. 2003 May;98(5):1042-8. [PubMed]
Drs. Babenko and Rampil
Phyathai Restaurant
Remi + Kids = Tolerance?
Dr. Babenko presented a good review of the article. From our discussion, we saw that there were various issues with the paper. An additional medication, fentanyl, was needed to treat the effects the test drug (remifentanyl). This could lead to increased side effects. Also, the measure of pain used in this study could be criticized. An observer assessed the pain so it is hard to tell if that was truly painful to the child or just a manifestation of restlessness. Admittedly, it is difficult to study this perfectly. An additional weakness and limitation in the design of the study was the small number of subjects, 60.
We reviewed the statistics. One positive aspect is that the researchers tested their data for normality first. If it were not normal then they would need to use a nonparametric test. However, this study did not segregate patients by age. Ages ranged from 1 to 5 years old. The difficulty of recruiting enough subjects for this type of procedure may have been the limiting factor that prevented a study of the age-dependence of the effect.
Intraoperative infusion of 0.6-0.9 µg·kg(-1)·min(-1) remifentanil induces acute tolerance in young children after laparoscopic ureteroneocystostomy. Kim SH, Lee MH, Seo H, Lee IG, Hong JY, Hwang JH. Anesthesiology. 2013 Feb;118(2):337-43. [PubMed]

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