Practice-Changing Articles
From My wiki
Lack of Accuracy of Point of Care Glucometers (April 2010)
If you have ever treated introoperative hyper or hypoglycemia based on a point of care glucometer, this is mandatory reading. Essential review of the technology behind (and potential faults related to) point of care glucometers. Indeed, some models may be off by as much as 30 mg/dL. Reviews accuracy of multiple manufacturers, as well as points towards potential sources of error (anemia, polycythemia, hyper/hypoxemia, hypotension, shock, various drugs). Particularly worrisome is the potential inaccuracy in the hypoglycemic range (would you treat 75 mg/dL? What if it was really 45 mg/dL?). Could this be a problem with previous studies of glucose control which allowed the use of point-of-care devices (ex. NICE-SUGAR)? What do you care about more, arterial glucose or venous? All addressed by this article [Rice MJ et al. Anesth Analg. 110: 1056, 2010].
A discussion with the author can be found on the OpenAnesthesia Audio/Video section. Direct link is Audio/Video#April_2010:_Glucose_Measurement_in_the_Operating_Room:_More_Complicated_than_It_Seems archives.
Updated ACC/AHA Guidelines (November 2009)
Major changes from 2007 include removal of "...patients undergoing vascular surgery who are at high cardiac risk..." from Class I recommendation (as of 2009 the only class I indication for perioperative beta blockade is in patients already taking beta blockers (Level of Evidence C [only very limited populations evaluated and/or based on expert opinion, case studies, or "standard of care"]), and added that "routine administration of high-dose beta blockers in the absence of dose titration is not useful and may be harmful to patients not currently taking beta blockers who are undergoing non-cardiac surgery (level of evidence, B) [Article in Circulation: Fleischmann KE et al. Circulation 120: 2123, 2009]
NICE-SUGAR Data on Glucose Control in the ICU (March 2009)
Multi-center, multi-ICU, prospective, randomized, controlled trial (n = 6104) comparing intensive (goal 81-108 mg/dL) versus relaxed (goal < 180 mg/dL) glucose management in adults expected to stay in an ICU for 3 or more days. Importantly, the OR for death in the intensive control group was 1.14 (CI 1.02 to 1.28, p = 0.02). Of note, unlike Van den Bergh's trial, this study did not require all measurements to be made with an arterial blood gas analyzer [NICE-SUGAR Study Investigators. NEJM 360: 1283, 2009]
Mayo Cardiac Stent Data (October 2008)
Retrospective study of 899 patients at Mayo Clinic showed that major adverse cardiac events (MACE) after non-cardiac surgery (NCS) decreased with increased time post-BMS placement – 10.5% (< 30d), 3.8% (31-90d), 2.8% (> 90d) and that bleeding complications were not associated with antiplatelet therapy within a week of surgery [Nuttal et. al. Anesthesiology 109: 588, 2008]
Retrospective study of 520 patients at Mayo Clinic suggested that MACE after NCS was independent of time post-placement – 6.4% (0-90d), 5.7% (91-180d), 5.9% (181-365d), and 3.3% (>356d, p = 0.727) and that bleeding complications were not associated with antiplatelet therapy within a week of surgery [Rabbitts et. al. Anesthesiology 109: 596, 2008]. Note, that the study was “underpowered” to detect observed differences (6% vs 3.3% mortality), which are presumably clinically significant
Perioperative Beta Blockade (May 2008)
Landmark study suggesting that indiscriminate perioperative beta blockade may be harmful. Criticized because of the high doses and non-specfic nature in which beta blockers were employed [POISE Study Group. Lancet 371: 1839, 2008]. Still, as a result of this trial the ACC/AHA practice guidelines have revised their recommendations such that the only class I indication for perioperative beta blockade is in patients already taking beta blockers (Level of Evidence C [only very limited populations evaluated and/or based on expert opinion, case studies, or "standard of care"]) [Article in Circulation: Fleischmann KE et al. Circulation 120: 2123, 2009]. For a fascinating discourse on this topic, please see our Podcast interview of Dr. London (available for free on iTunes), which you may also listen to here:
Intensive Intraoperative Insulin Therapy (February 2007)
Aggressive treatment of hyperglycemia in cardiac surgery patients does not improve mortality and in fact increases the incidence of stroke (p = 0.020) and death (p = 0.061) [Gandhi GY et. al. Annals of Internal Medicine 146: 233, 2007]. Largest intraoperative study to address this issue.
Methylene Blue (Multiple, Review)
Biochemical Concepts
Vascular smooth muscles are affected by both agonists (which induce contraction) and antagonists (which induce relaxation). The classic example of agonists/antagonists is epinephrine, whose actions depend on the binding site (which is dependent on the concentration, with beta agonism predominating at low doses, and alpha agonism taking over at higher doses). Alpha-1 receptors, when stimulated, activate the inositol-phospholipid-calcium pathway, leading to the production of IP3 (which causes calcium release from the ER) and the activation of DAG (which activates protein kinase C [PKC]), both of which lead to smooth muscle contraction and vasoconstriction. Beta-receptors, by contrast, work on smooth muscle cells via the cAMP pathway – binding of the beta-receptor results in the activation of adenylyl cyclase and subsequent production of cAMP, which produces smooth muscle relaxation. Both alpha and beta adrenergic receptors (which work through the IP3/DAG and cAMP pathways) are G-protein mediated
Analogous to cAMP-mediated vasodilation due to beta-receptor activation, nitric oxide (produced from arginine via nitric oxide synthase) is able to induce smooth muscle relaxation via production of cGMP (cAMP and cGMP seem to have similar effects). In this case, nitric oxide activates guanylyl cyclase to produce cGMP, which activates protein kinase G (PKG), leading to smooth muscle relaxation. Importantly, nitric oxide production can be triggered by inflammatory mediators (bradykinin, interleukins, cytokines) that result from trauma, pharmacologic agents, shear stress, or cardiopulmonary bypass, thus implicating the NO/cGMP pathway in vasoplegia following bypass, sepsis, etc.
Methylene blue has a variety of effects, several of which inhibit NO-induced vasodilation – inhibition of guanylate cyclase [Cruetter CA et al. Can J Physiol Pharmacol 59: 150, 1981], as well as both endogenous and inducible nitric oxide synthase [Mayer B et al Eur Heart J 14: 22, 1993; Keaney JF et al. Circ Res 74: 1121, 1994; Lomniczi A et al. Neuroimmunomodulation 8: 122, 2000] can potentially counteract the effects of inflammatory mediators on vascular smooth muscle in a variety of physiologic states.
Clinical Applications of Methylene Blue
Septic Shock
Kirov et al. randomized twenty patients with septic shock to methylene blue (2 mg/kg followed by 0.25-2 mg/kg/hr, titrated to MAP 70-90) versus normal saline in addition to standard ionotropes. Methylene blue reduced the requirement for norepinephrine, epinephrine, and dopamine by as much as 87%, 81%, and 40%, respectively. At the end of infusion, LVSWI had increased by 32% in the methylene blue group, whereas in the control group LVSWI fell by as much as 40% below baseline (p < .05). Methylene blue maintained DO2, which fell by 69% in the saline group (p < 0.05). The mortality rate in the methylene blue arm was 58%, as compared to 75% in the saline group (p = 0.65) [Kirov et al. Crit Care Med 29: 180, 2001]
Liver Transplant
Koelzow et. al. investigated the use of methylene blue in ischemia reperfusion syndrom (IRS) during orthotopic liver transplantation (OLT). 36 patients undergoing OLT were randomized to either 1.5 mg/kg methylene blue or saline prior to graft reperfusion. The methylene blue group had higher MAPs (increased by 5% versus fell by 12%, p = 0.035), higher cardiac indices (7.4 vs. 6.2 L/min/m2, p = 0.03 at 30 minutes and 7.6 vs. 6.3 L/min/m2, p = 0.04 at 60 minutes), required less epinephrine (p = 0.02), and no effect on SVR or CVP. One hour after infusion, lactate levels were lower in the methylene blue group (p = 0.03) [Koelzow H et al. Anesth Analg 94: 824, 2002; FREE Full-text at Anesthesia & Analgesia]
Cardiopulmonary Bypass
Levin et al. randomized 56 vasoplegic patients (defined as hypotensive, with low filling pressures, low peripheral vascular resistance, and elevated or normal cardiac index despite significant vasopressor requirements) following cardiopulmonary bypass to 1.5 mg/kg of methylene blue versus placebo. Patients who received methylene blue showed a significant reduction in mortality (0% versus 21.4% [6 of 28 patients], p = 0.01), as well as in the incidence of renal failure (0 vs. 14%, p = 0.05), respiratory failure (0 vs. 14%, p = 0.05), supraventricular tachycardias (7% vs 28%, p = 0.03), sepsis (0% vs 25%, p = 0.005), and multiorgan failure (0% vs 25%, p = 0.005). No episode of vasoplegia lasted longer than 2 hours in the methylene blue groups, whereas in the placebo groups vasoplegia lasted up to 48 hours [Levin RL et al. Ann Thorac Surg 77: 496, 2004]
Ozal et al. randomized patients “at risk” for post-operative vasoplegia (undergoing CABG procedures and having taken ACE-inhibitors, calcium channel blockers, or heparin preoperatively) to 2 mg/kg methylene blue versus nothing (no placebo). The two groups differed in the incidence of vasoplegia (0% vs. 26%, p < 0.001), average ICU stay (1.2 vs. 2.1 days, p < 0.001), and average hospitalization (6.1 vs. 8.4 days, p < 0.001). The methylene blue group required less volume (1.57 L vs. 1.75 L, p = 0.024), displayed higher SVR (p < 0.001), had lower ionotropic requirements to come off of bypass (p < 0.001), and had higher urine output during bypass (738 vs 631 cc, p = 0.019) despite a trend towards lower time on bypass (68.5 vs 70.7 minutes, p = 0.123) [Ozal E et al. Ann Thorac Surg 79: 1615, 2005]
Maslow et al. randomized 31 patients who had received ACE-inhibitors and who were undergoing cardiopulmonary bypass (CPB) to 3 mg/kg of methylene blue versus saline following CPB and cardioplegia. Methylene blue increased MAPs (statistically significant at post-drug and 20-40 mins of CPB timepoints, but not at 60 minutes of CPB or post-CPB) and SVR (significant up to 40 minutes), thus the effects appeared to last only ~ 40 minutes. Methylene blue administration resulted in lower phenylephrine and norephrine requirements, and resulted in lower serum lactate levels. While the methylene blue group had higher cardiac output post-bypass (6.1 L/m vs. 5.6 L/min), this did not reach statistical significance [Maslow AD et al. Anesth Analg 103: 2, 2006; FREE Full-text at Anesthesia & Analgesia]
Futility of FFP Transfusion for Mild Coagulation Abnormalities (August 2006)
Ever been asked to transfuse fresh frozen plasma to "correct" an INR of 1.8 or less? Given the cost and potential risks associated with the transfusion of blood products, you might be interested in knowing just how likely one or more units of FFP are to normalize an INR or 1.8 or less. The answer? Based on a retrospective audit of 1091 transfusions at Massachusetts General Hospital, less than 1% [Abdel-Wahab OI et al. Transfusion 46: 1279, 2006]. And, while transfusion of FFP gives you a 15% of correcting INR halfway to normal, given that the utility of INR is in question anyway [Charpak Y et. al. Can J Cardiol 2: 134, 1986; Manning SC et. al. Int J Pediatr Otorhinolaryngol 13: 237, 1987; Darcy MD et. al. Radiology 198: 741, 1996], Abdel-Wahab's data should certainly give you pause
