Anesth Analg 2008; 107:725-726
© 2008 International Anesthesia Research Society
doi: 10.1213/ane.0b013e31817c73b3
LETTER TO THE EDITOR
Section Editor:
Lawrence Saidmanm
Judgment and Risk to Patient in Study Design
Jeff E. Mandel, MD, MS,
Gary R. Lichtenstein, MD,
David C. Metz, MD,
David A. Katzka, MD,
Gregory G. Ginsberg, MD, and
Michael L. Kochman, MD
University of Pennsylvania Medical Center; Philadelphia, Pennsylvania; jemandel{at}verizon.net
In Response:
The design of the study was chosen to permit a double-blind comparison of fentanyl-midazolam to propofol-remifentanil (PR).1 The use of patient-controlled sedation in both arms was necessary to permit blinding. The intent of the study was to examine the improvement in facility efficiency at equivalent endpoints of patient, nurse, and endoscopist satisfaction. The study demonstrated that significant improvements could be obtained with this approach, but anesthesiologist rescue was necessary in 2 of 25 cases. We chose to compare these groups because fentanyl-midazolam is the existing standard for gastroenterologist-directed sedation in our institution, and PR is the standard approach of the principal investigator. We had considerable experience upon which to draw in designing the protocol. There is also considerable interest among the gastroenterologists in alternatives to midazolam-fentanyl sedation.
The issue of patient selection was raised by one of the reviewers of the article and resolved to the satisfaction of the editor. We recruited patients from the elective outpatient colonoscopy population. Patients with significant comorbidity were therefore not typically scheduled for gastroenterologist-directed sedation. Women of childbearing potential were excluded, as were prisoners, minors, and patients judged unable to understand the concept of the patient-controlled sedation. There were a small number of patients deemed PS 3 by the principal investigator. The demographics were consistent with historical averages for colonoscopy at our institution.
The endoscopy RNs were instructed to intervene with verbal or physical stimulation for hemoglobin oxygen desaturation, but were not expected to institute bag-mask ventilation. The anesthesiologist was required to intervene after 60 s. Although this might seem a dangerous practice to those only familiar with propofol as a single agent, the respiratory events associated with PR in small incremental doses are usually a lack of respiratory drive and are responsive to verbal stimulus, and not requiring maneuvers to overcome obstruction. In general, when patients became unresponsive, it was a consequence of one button press too many or a cessation of endoscopic stimulation. Patients were rarely unable to co-operate with a command to breathe for more than 90 s, and never pressed the button during hemoglobin-desaturation. The rate of desaturation seen in our study was less than the principal investigator observes in patients undergoing sedation by anesthesia residents. There were no patients who repeatedly exhibited hemoglobin desaturation of <60 s, or who spent significant periods at Spo2 of 86%. We stated that the safety endpoint was chosen to simulate a process in which an anesthesiologist in the immediate vicinity would respond to an episode of desaturation, and we believe that we have established that this technique should not be contemplated by practitioners not prepared to meet this standard.
We are unaware of any study that establishes the safe limits of hypoxia and considerable data from high altitude medicine and sleep labs suggest that Spo2 <85% is common.2,3 We do not advocate hypoxia, but there is little evidence to suggest that 60 s of hemoglobin desaturation is associated with any significant morbidity or sequelae in the patient population studied.
The protocol and informed consent were approved by the IRB of the University of Pennsylvania. The protocol underwent review at the highest levels of the health system, including the Chief Safety Officer and the chair of the Committee on Medical Ethics. The protocol explicitly stated that a single adverse event leading to tracheal intubation would halt the study pending review by the Chairman of Anesthesiology and Critical Care. The risks and benefits of the study including the risk of hypoxia were explained to all patients by the principal investigator. The principal investigator met regularly with the Data Safety Monitor and filed Adverse Event reports in a timely fashion. There was no outside funding utilized in the study. We and the IRB believe that every attempt was made to conduct the study ethically, but welcome suggestions on how we could improve.
We do not represent our protocol as a recipe for standard clinical practice. It is a single piece of evidence in an effort to devise a safe practice of sedation for colonoscopy that permits anesthesiologists to maintain involvement in a clinical area that is rapidly slipping irretrievably from our grasp.
REFERENCES
- Mandel JE, Tanner JW, Lichtenstein GR, Metz DC, Katzka DA, Ginsberg GG, Kochman ML. A randomized, controlled, double-blind trial of patient-controlled sedation with propofol/remifentanil versus midazolam/fentanyl for colonoscopy. Anesth Analg 2008;106:434–9[Abstract/Free Full Text]
- Salvaggio A, Insalaco G, Marrone O, Romano S, Braghiroli A, Lanfranchi P, Patruno V, Donner CF, Bonsignore G. Effects of high-altitude periodic breathing on sleep and arterial oxyhaemoglobin saturation. Eur Respir J 1998;12: 408–13[Abstract]
- Valencia-Flores M, Rebollar V, Santiago V, Orea A, Rodriguez C, Resendiz M, Castano A, Roblera J, Campos RM, Oseguera J, Garcia-Ramos G, Bliwise DL. Prevalence of pulmonary hypertension and its association with respiratory disturbances in obese patients living at moderately high altitude. Int J Obesity 2004; 28:1174–80[Web of Science][Medline]
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