BETA BLOCKADE: IT S NOT JUST FOR CARDIOLOGY PATIENTS
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1 BETA BLOCKADE: IT S NOT JUST FOR CARDIOLOGY PATIENTS Sympathetic Receptors Agonists Kristan Staudenmayer, M.D. M.S. Assistant Professor of Surgery Stanford University May 31, 2012 Antagonists Beta Blockade Tip of the iceberg Objectives Clinical Scenarios Traumatic Brain Injury Burns/Metabolic Others: Wound healing, Sepsis, Bone marrow supression, sepsis, pain, PTSD For TBI and Burns The science Indications
2 How did it start? BETA BLOCKADE IN TRAUMATIC BRAIN INJURY Possible benefits for beta blockers first described for subarachnoid hemorrhage. Researchers sought to identify mechanisms to prevent vasospasm Subarachnoid Hemorrhage Good to prevent vasospasm? The Lund Therapy Physicians at the University Hospital in Lund, Sweden Proposed that death after brain injury was not only due to primary injury, but secondary preventable injury as well Recommended a multi drug therapy, including adrenergic blockade, to improve cerebral blood flow
3 ICP reduction achieved within a few hours Of the 11 patients, 2 died Other Lund Therapy Studies Limitations: All are non randomized Ecker et al. historic control groups approximately 10years older Naredi et al. have no control groups Conclusions: 1.Requires more rigorous investigation than what has been done, but 2.Suggested that adrenergic blocking agents were tolerated Retrospectively evaluated whether beta blocker use was safe in all trauma patients, and especially head injured patients
4 All TBI patients with head AIS >=3 were evaluated Excluded stays <4 days >30 Total n=420; 174 were exposed to beta blockers What to make of the beta blockers? Raw RR Adjusted RR Prop. Adjusted RR Prop. Score Quintile RR Seems to be safe Most likely multi factorial impact on outcomes Relevance in the context of current management principles not studied
5 What needs to be done? Identify specific indications in TBI Which beta blocker should be used? Selective vs. non selective? Timing for initiation? BETA BLOCKERS AND METABOLISM AFTER BURN INJURY Metabolism, Injuries, and Burns Severe injuries increased metabolism Burns make for a quantifiable dose of injury Hyper metabolism after burn injury 1. Surface temperature 2. Catecholamines 3. Nutrition 20 >45% TBSA burn patients and 4 controls
6 Found that catecholamines mediate the hyper metabolic response to burn injury Alpha and beta blockade decreased metabolic rates (70 Kcal/m2/hr to 57 Kcal/m2/hr) Epinephrine infusion increased the metabolic rate Randomized controlled trial Enrolled 25 children >40%TBSA burns Treatment group: Propranolol to decrease resting HR by 20% Treatment time 2 weeks Compared change from baseline fat free mass Control patients lost 9% mass vs. none in the treatment group Hyper catabolism after Injury Herndon et al Ann Surg 1994 Arch Surg 2001 NEJM Morio et al Ann Surg Wolfe et al NEJM Gore et al Ann Surg From Pereira et al., Advances in Surgery, 2005
7 129 Adult burn patients Cohorts divided into: 1. No beta blockers 2. Patients on beta blockers before injury 3. Patients who were initiated on therapy after injury (usually for a complication) Any harm at all? Retrospective trauma registry review of all patients >=65 admitted to a single trauma center from Evaluated relationship between pre injury beta blockade and outcomes Total 1,479 met inclusion criteria, 273 on beta blockers before their injury
8 How are Beta Blockers Being Used? Adjusted odds for death for patients on pre injury BB All patients 1.0 NS Difference Head Injured Patients 0.7 NS Patients without Head 2.1 P<0.05 Injuries Adjusted for age, ICU admission, ISS, heart rate, warfarin, renal failure Are they used in all injured patients? Are they used in all burn patients? Are they used for in all pediatric burn patients? What about pediatric burns >40% TBSA? No, not really to all questions Beta Blocker Use Overall Hospitals P value WHERE IS THIS ALL GOING? Small burn (<10% TBSA) Medium burn (10 30% TBSA) Large burn >30% TBSA 2% 1% 3% 3% p<0.01 3% 1% 8% 2% NS 37% 48% 39% 24% p<0.01
9 Where are we going? This likely represents the tip of the iceberg The sympathetic nervous system is intimately tied to many aspects of critical care beyond the heart Manipulation of this system is easy, and may be safer in critical illness than we have thought. Conclude We will likely see the role of beta blockade grow in the next few years Disease models likely to be featured include: TBI Metabolism after injury Sepsis
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