Dept Of Anesthesiology & Critical Care, University Of Pennsylvania School Of Medicine

Bad news for tight intraoperative glucose control

Dr. Kofke calls our attention to this prospective randomized study of tight intraoperative glucose control using insulin infusion compared to “conventional” management with tight control in both groups during the post operative period.  Four hundred cardiac surgery patients were randomly assigned to tight glycemic control (blood glucose levels between 80 – 100 mg/dl) during surgery or conventional glucose control.    Patients who did not become hyperglycemic during surgery were not included in the analysis.  Pre operatively the glucose levels were similar in both groups.  At the conclusion of cardiopulmonary bypass the mean blood glucose level in the tight control group was significantly lower (123 mg/dl) compared to 148 mg/dl in the conventional glucose control group.  All patients in the intensive treatment group received insulin during surgery and 15% of the patients in the conventional therapy group received insulin.  At the end of 24 hours in the ICU the mean glucose levels were the same in both groups (about 106 mg/dl, mean).  The two groups did not differ in the primary composite endpoint of sternal infection, death, prolonged ventilation, cardiac arrhythmias, stroke or renal failure.  Nor did investigators find a direct benefit from intraoperative from intensive insulin therapy for and of the individual components of the composite end point.  In fact the reverse result was obtained.  The intensive treatment group had significantly more strokes (8 vs. 1) and deaths (4 vs. 0) than the conventional treatment group.  There was no treatment effect for length of stay in the ICU or hospital.  The authors note that this does not directly contradict prior findings of benefits from tight glucose control as the key studies involved tight control vs. conventional control during the entire period from OR through ICU.  It is possible that tight glucose control during the relatively brief period of surgery is not as important as tight glucose control during the longer post operative period.  Gandhi GY et al: Intensive intraoperative insulin therapy versus conventional glucose management during cardiac surgery.  Ann Intern Med 2007;146:233-243

Dr. WA Kofke is Professor of Anesthesiology at UPENN

David Smith, M.D., Ph.D.

Race and socio – economic status influence acceptance of post operative epidural analgesia

Ochroch and associates (Anesth Analg 2007;105:1787) used a survey of patients scheduled for elective surgery to determine rates of acceptance of post operative epidural analgesia.  Over a four month period a trained research technician contacted the patients the day prior to their scheduled admission and then conducted a standard survey by telephone.  3739 patients were called at home, 1265 were contacted and 1193 consented to participate in the study.  64% of the study participants said that they would accept an epidural if recommended by an anesthesiologist and 36% said they would refuse.  The rate of acceptance increased to 78% if the epidural was recommended by both the surgeon and anesthesiologist with 22.5% still refusing.  A univariate logistic regression showed that patients with higher incomes, more education and who where employed full or part time were more likely to accept an epidural.  African Americans were far less likely then Caucasians to accept an epidural.  When controlling for gender, education level, employment type income and marital status, African American race predicted refusal of epidural analgesia. (OR 0.58, 95 % 0.32 – 0.78)  The authors attempted to determine some of the reasons for refusal but were unable to do so.  Of concern then is a group of patients who for some reason absent themselves from a proven form a post operative pain therapy that may have benefits with respect to reduced pain and improved recovery.  Of interest, from my observations, is the high acceptance of epidural analgesia on the HUP labor floor in a patient population that has a large number of African Americans (DSS comment).

Edward Andrew Ochroch M.D., MSCE is Associate Professor of Anesthesiology and Critical Care at the Hospital of the University of Pennsylvania

David S. Smith, M.D., Ph.D.

Cognition despite a persistent vegatative state

Dr. Kofke sumarizes Dr Adrian M Owen's  (University of Cambridge in the United Kingdom) SNACC (Society of Neurosurgical Anesthesia and Critical Care) annual meeting presention on functional Magnetic Resonanace Imaging (fMRI) in patients in a persistent vegetative state (see the Etherway http://mkeamy.typepad.com/anesthesiacaucus/2007/11/awareness-in-th.html).    Dr. Owen's work shows clear evidence of cognition in some of these patients.  This work should cause a general re-evaluation of what is and what is not awareness even in the severely brain injured.

W A Kofke is Professor of Anesthesiology and Critical Care at the University of Pennsylvania and Director of the Neurosurgical Anesthesia service.   

Pain relief after colorectal surgery

Epidural analgesia after colorectal surgery was examined via a meta-analysis of 16 trials published between 1987 and 2005.  Epidural analgesia compared to parenteral opioid analgesia provided significantly reduced pains scores and decreased duration of ileus.  There was an increase in the incidence of pruritus, urinary retention and hypotension with epidural analgesia.  There was no difference in duration of hospital stay (Marret E et al: Meta-analysis of epidural analgesia versus parenteral opioid analgesia after colorectal surgery.  B J Surg 2007;94:665-673.

David S. Smith, M.D., Ph.D.

Truth in Science

The Wall Street Journal (September 14, 2007) contains the headline “Most Science Studies Appear to Be Tainted by Sloppy Analysis” The article is based on the work of epidemiologist John Ioannidis who has claimed that “most publish research findings are wrong (Why Most Published Research Findings Are False; PLoS medicine 2005;2:696-701).  He notes that the probability of a true finding is related to the size of the study, the magnitude of the effect size difference, the number of tested relationships, the number of other studies on the same or a similar question, and the flexibility of design.  The author notes that the prevalent practice of examining a study in isolation from all of the other work in the same area greatly increases the probability that a given result is due to random fluctuation.

David S. Smith, M.D., Ph.D.

Dr Kofke Discusses Deep Circulatory Arrest and Brain Ischemia

In the Ether Way Blog Andy Kofke reviews the UPENN experience on brain preservation during circulatory arrest for aortic arch surgery and how the successes for this operation might apply to other types of surgery that produce a risk for cerebral ischemia (http://mkeamy.typepad.com/anesthesiacaucus/2007/09/deep-hypothermi.html)

Publications 2006 Department of Anesthesiology and Critical Care

Armstead W M: Association between intravascular coagulopathy and outcome after traumatic brain injury.[comment]. Neurology India 2006;54: 347-8

Armstead W M: Differential activation of ERK, p38, and JNK MAPK by nociceptin/orphanin FQ in the potentiation of prostaglandin cerebrovasoconstriction after brain injury. European Journal of Pharmacology 2006;529: 129-35

Armstead W M, Nassar T, Akkawi S, Smith D H, Chen X-H, Cines D B, Higazi A A-R: Neutralizing the neurotoxic effects of exogenous and endogenous tPA. Nature Neuroscience 2006;9: 1150-5

Atkins J H, Johansson J S: Technologies to shape the future: proteomics applications in anesthesiology and critical care medicine. Anesthesia & Analgesia 2006;102: 1207-16

Augoustides J G, Pochettino A, Ochroch E A, Cowie D, Weiner J, Gambone A J, Pinchasik D, Bavaria J E, Jobes D R, Augoustides J G T, Pochettino A, Ochroch E A, Cowie D, Weiner J, Gambone A J, Pinchasik D, Bavaria J E, Jobes D R: Renal dysfunction after thoracic aortic surgery requiring deep hypothermic circulatory arrest: definition, incidence, and clinical predictors. Journal of Cardiothoracic & Vascular Anesthesia 2006;20: 673-7

Augoustides J G T, Hosalkar H H, Milas B L, Acker M, Savino J S: Upper gastrointestinal injuries related to perioperative transesophageal echocardiography: index case, literature review, classification proposal, and call for a registry. Journal of Cardiothoracic & Vascular Anesthesia 2006;20: 379-84

Barnett R: Pro: Veno-veno bypass should routinely be used during liver transplantation.[see comment]. Journal of Cardiothoracic & Vascular Anesthesia 2006;20: 742-3

Byrem W C, Armstead S C, Kobayashi S, Eckenhoff R G, Eckmann D M: A guest molecule-host cavity fitting algorithm to mine PDB for small molecule targets. Biochimica et Biophysica Acta 2006;1764: 1320-4

Carnini A, Eckenhoff M F, Eckenhoff R G: Interactions of volatile anesthetics with neurodegenerative-disease-associated proteins. Anesthesiology Clinics 2006;24: 381-405

Churbanova I Y, Tronin A, Strzalka J, Gog T, Kuzmenko I, Johansson J S, Blasie J K: Monolayers of a model anesthetic-binding membrane protein: formation, characterization, and halothane-binding affinity. Biophysical Journal 2006;90: 3255-66

Cook-Sather S D, Litman R S: Modern fasting guidelines in children. Best Practice & Research Clinical Anaesthesiology 2006;20: 471-81

Cucchiaro G, Adzick S N, Rose J B, Maxwell L, Watcha M: A comparison of epidural bupivacaine-fentanyl and bupivacaine-clonidine in children undergoing the Nuss procedure. Anesthesia & Analgesia103: 322-7

Deutschman C S, Cereda M, Ochroch E A, Raj N R: Sepsis-induced cholestasis, steatosis, hepatocellular injury, and impaired hepatocellular regeneration are enhanced in interleukin-6 -/- mice.[see comment]. Critical Care Medicine 2006;34: 2613-20

Dominguez T E, Helfaer M A: Review of bispectral index monitoring in the emergency department and pediatric intensive care unit. Pediatric Emergency Care 2006;22: 815-21; quiz 822-4

Eckmann D M, Armstead S C: Influence of endothelial glycocalyx degradation and surfactants on air embolism adhesion. Anesthesiology 2006;105: 1220-7

Eckmann D M, Zhang J, Lampe J, Ayyaswamy P S, Eckmann D M, Zhang J, Lampe J, Ayyaswamy P S: Gas embolism and surfactant-based intervention: implications for long-duration space-based activity. Annals of the New York Academy of Sciences 2006;1077: 256-69

Frey T K E, Chopra A, Lin R J, Levy R J, Gruber P, Rheingold S R, Hoehn K S: A child with anterior mediastinal mass supported with veno-arterial extracorporeal membrane oxygenation. Pediatric Critical Care Medicine 2006;7: 479-81

Gavrin J R: The American Medical Association "Pain Management: the Online Series". Journal of Pain & Palliative Care Pharmacotherapy 2006;20: 71-7

Gavrin J R: Palliative care. Anesthesiology Clinics 2006;24: xv-xvi

Gavrin J R: A prototypical gateway to the World Wide Web: Making sense of pain relief. Journal of Pain & Palliative Care Pharmacotherapy 2006;20: 29-31

Hecker J G, Laslett L, Campbell E, Nunnally M, O'Connor A, Ellis J E, Frogel J K, Fleisher L A: Case 2-2006: Catastrophic cardiovascular collapse during carotid endarterectomy. Journal of Cardiothoracic & Vascular Anesthesia 2006;20: 259-68

Huh J W, Franklin M A, Widing A G, Raghupathi R: Regionally distinct patterns of calpain activation and traumatic axonal injury following contusive brain injury in immature rats. Developmental Neuroscience 2006;28: 466-76

Johansson J S: Central nervous system electrical synapses as likely targets for intravenous general anesthetics.[comment]. Anesthesia & Analgesia 2006;102: 1689-91

Kohl B A: Con: Should aspirin be continued after cardiac surgery in the setting of thrombocytopenia?[comment]. Journal of Cardiothoracic & Vascular Anesthesia 2006;20: 114-6

Levine G K, Deutschman C S, Helfaer M A, Margulies S S: Sepsis-induced lung injury in rats increases alveolar epithelial vulnerability to stretch.[see comment]. Critical Care Medicine 2006;34: 1746-51

Li M, Ratcliffe S J, Knoll F, Wu J, Ances B, Mardini W, Floyd T F: Aging: impact upon local cerebral oxygenation and blood flow with acute isovolemic hemodilution. Journal of Neurosurgical Anesthesiology 2006;18: 125-31

Longnecker D E: Resident duty hours reform: are we there yet?[comment]. Academic Medicine 2006;81: 1017-20

Miksa D, Irish E R, Chen D, Composto R J, Eckmann D M: Dextran functionalized surfaces via reductive amination: morphology, wetting, and adhesion. Biomacromolecules 2006;7: 557-64

Muravchick S, Levy R J: Clinical implications of mitochondrial dysfunction. Anesthesiology 2006;105: 819-37

Ochroch E A, Gottschalk A, Troxel A B, Farrar J T: Women suffer more short and long-term pain than men after major thoracotomy. Clinical Journal of Pain 2006;22: 491-8

Pan J Z, Wei H, Hecker J G, Tobias J W, Eckenhoff R G, Eckenhoff M F: Rat brain DNA transcript profile of halothane and isoflurane exposure. Pharmacogenetics & Genomics 2006;16: 171-82

Sadhasivam S, Ganesh A, Robison A, Kaye R, Watcha M F: Validation of the bispectral index monitor for measuring the depth of sedation in children.[see comment]. Anesthesia & Analgesia 2006;102: 383-8

Xi J, Liu R, Rossi M J, Yang J, Loll P J, Dailey W P, Eckenhoff R G: Photoactive analogues of the haloether anesthetics provide high-resolution features from low-affinity interactions. ACS Chemical Biology [Electronic Resource] 2006;1: 377-84

The conflict of organizational ethics and societal rule of law

Nontherapeutic quality improvement: The conflict of organizational ethics and societal rule of law

Michael A. Rie, MD; W. Andrew Kofke, MD, MBA, FCCM

Objective: Critical care ethics focuses largely on patient autonomy. Cost containment is necessary but requires rationing and limitations on a patient’s right to consume beneficial services. No laws address a process of autonomy rights limitation to consume resources in the intensive care unit. We analyzed the frictional interface between necessary cost containment as a quality improvement activity contrasted with individual autonomy in the context of the evolution of research ethics.

Data Sources and Synthesis: Scholarly books, peer-reviewed articles, congressional record, legal sources, the World Wide Web, and the National Archives and Records Administration were evaluated in the context of current cost-containment– driven nontherapeutic quality improvement activities.

Principal Findings: Three generations in the evolution of human research ethics are identified: 1) Hippocrates to Nuremberg Code, 2) Nuremberg to Belmont, and 3) Belmont to present.  Similar ethical lapses, which place the individual at risk without disclosure for the good of future patients, have arisen recurrently in the course of history and continue presently when nontherapeutic quality improvement activities are framed as a human research activity with essentially no ethical oversight. Consequently, the fiduciary obligations of professionals and their employer institutions to their mutual patients may be at odds, creating complex layers of conflicted decision making. Nonetheless, professional Hippocratic duty to “the patient” must be congruent with the organizational ethos of limited funding “stewardship” to produce meaningful patient care. Medicine’s integrity is legally protected and mandated under the state interests (parens patria doctrine) of the common law.

Conclusion: When hospitals (society and its health insurance methods) fail to ration transparently under “cost-containment ethics,” they threaten the ethical integrity of the medical profession.  (Crit Care Med 2007; 35[Suppl.]:S66–S84)