Disclosure. Objectives 9/13/2018. NIA/NIH 1R03AG (PI-Bentov) More than Start low go slow. start low go slow

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Sedation and analgesia in geriatric trauma Sept 2018 Itay Bentov MD PhD Disclosure NIA/NIH 1R03AG042353 (PI-Bentov) More than Start low go slow start low go slow Objectives List age-related physiologic changes Relate the role of anesthetic management to outcomes improvement Modify anesthetic drugs dose in the aged. (what anyone who provides anesthesia/ sedation should know). 1

Dispute with daughter Cordelia followed by GLF. Hx -HTN, GERD, dementia? ( stoops to folly ) ECG -LVH CBC Hct-29 Imaging -# Rt hip (>250,000/year in the US) K. Lear 76 yomale The Tragedy of K Lear one year mortality for hip fractures is between 14-58%!!! (Geriatr Orthop Surg Rehabil. 2010 Sep; 1(1): 6 14) Delirium(Agitation or withdrawal) 10-15% of surgical patients >65yo 30-50% if undergoing cardiac or orthopedic surgery -> prolonged hospitalization, loss of functional independence, reduced cognitive function, and death. The annual cost of delirium in the US is $150 billion (Postoperative delirium in older adults: best practice statement from the American Geriatrics Society 2015) Potentially modifiable risk factors for delirium Nat Rev Neurol. Apr 2009; 5(4): 210 220. Sensory impairment Immobilization Medications (for example, sedative hypnotics, narcotics, anticholinergic drugs) Intercurrent illness (for example: anemia, dehydration, fracture or trauma) Surgery Environment Pain Emotional distress Sustained sleep deprivation 2

Reduced postoperative delirium in hip fracture patients (50%->32% or 29%->12%) J Am GeriatrSoc. 2001;49(5):516-22. Maintain blood pressure Maintain O2 saturation Maintained Hct > 30% Mobilized patients ASAP Provided appropriate environmental stimulation Minimized benzodiazepines, anticholinergics, antihistamines, meperidine What can we do? Oxygenation Fluids temperature Arch Surg. 2009 Apr;144(4):359-66. Anesth Analg. 2012;114(2):334-42. N Engl J Med. 1978;298(12):659-68. N Engl J Med. 2000;342(3):161-7. JAMA 2005; 294:2035-42. Eur Respir J. 1996;9(12):2573-7. Microcirculation 2006; 13: 289 299 Am J Pathol. 1999;154(1):301-9 JAMA. 1999;281(11):1022-9. Surgery. 2003;133(1):49-55 Ann Surg. 2003;238(5):641-8. N Engl J Med. 1997;336(24):1730-7 Anesthesiology. 1992;77(2):252-7. N Engl J Med 1996; 334:1209-15 Lancet 2001; 358:876-80 Front Biosci. 2010;15:718-39. Anesthesiology. 1995;83(6):1162-6. Anaesthesia. 1986 Apr;41(4):363-9. Anesth Analg. 2005;100(4):1093-106. Anesth Analg. 2006;102(2):344-6 Thermoregulatory responses are decreased in the aged. Clinical signs (such as shivering) are absent. Rewarming of the older patient takes significantly longer than younger adults. OccupEnviron Med 2007; 64: 93-100 Anesthesiology 1995; 83: 1162-6, AnesthAnalg1997; 84: 1029-33, Anesthesiology 1993; 79: 465-9. Hypothermia 3

Regional anesthesia?!? No difference in various outcomes measures Anesthesiology 2000; 92: 947-57 When one finds a differencethere are usually study design issues: Neuroaxialanesthesia (epidural or spinal anesthesia) for total hip or knee replacement was associated with a lower risk of SSI! however - Retrospective analysis GA group was older and with more comorbidities Anesthesiology 2010; 113: 279-84 Regional versus General Anesthesia for Promoting Independence after Hip Fracture (REGAIN): protocol for a pragmatic, international multicentre trial BMJ Open. 2016; 6(11) Age related changes in the skin Anesthesiology. 2014;120(3):760-72. Microcirculation is impaired Microvasc Res. 2015 Jul;100:25-31. 4

In the OR Alpine anesthesia Ventricular hypertrophy Diastolic dysfunction Connective tissue changes Loss of elasticity Loss of SA node cells, slowed conduction Myocyte death without replacement Enhanced sympathetic nervous system activity at rest (-> decreased response to adrenergic stimulation) Preoperatively: Beta blockers? POISE trial 190 hospitals, 23 countries, 8351 patients. (mean age 69y) extended-release metoprolol 2-4 h before surgery (n=4174) or placebo (n=4177) continued for 30 days. Less myocardial infarction (176 [4.2%] vs 239 [5.7%] patients; 0.73, 0.60-0.89; p=0.0017) However More deaths (129 [3.1%] vs 97 [2.3%] patients; 1.33, 1.03-1.74; p=0.0317) More stroke (41 [1.0%] vs 19 [0.5%] patients; 2.17, 1.26-3.74; p=0.0053) Lancet. 2008 371(9627):1839-47 5

Perioperative hypotension and discharge outcomes in non-critically injured trauma patients, a single center retrospective cohort study. Injury. 2017 Sep;48(9):1956-1963. Hypoxemia and Hypercarbia d/t increases in Shunt & Dead space Decreased VC Increased RV Decreased thoracic elasticity. Decreased elasticity of alveolar tissue Decreased strength and endurance of respiratory muscles Lad, if you go on to do Anaesthesia, you must use this thiopentone with great care and diligence because the Yanks killed more of their own at Pearl Harbor than did the Japanese in their attack in 1941. 6

Effect of Age on Drug Dosing Drug Bolus Administration Multiple Boluses or Infusion Commentsa Propofol 50% reduction, infusions beyond 50 min progressively 20 60% reduction, dose on lean brain sensitivity (by some reports), increase the time required to decrease the blood level by body mass, 1 mg/kg in very old decreased Vcen, slowed redistribution 50% (but effect-site levels may decrease faster in elderly) Etomidate 25 50% reduction #NAME? Midazolam Compared to age 20, modest reduction at age 60, 75% reduction at age 90 Similar to bolus (metabolic t½ longer, but not meaningful unless very large doses are used) brain sensitivity Morphine Probably 50% reduction. Peak Metabolite morphine-6-glucoronide Long effect-site equilibration time translates into very slow morphine effect is 90 min build-up requires prolonged morphine reduction in effect on termination of infusion (4 h for 50% (though half of peak effect at 5 use, but its renal excretion will make it reduction) min) very long-acting Fentanyl 50% reduction 50% reduction brain sensitivity, minimal changes in pharmacokinetics; delayed absorption from fentanyl patch Alfentanil, sufentanil 50% reduction 50% reduction Probably brain sensitivity, minimal changes in pharmacokinetics No studies on aging exist, but Compared with morphine, no active Hydromorphone assume increased potency in Assume 50% reduction metabolite, faster onset elderly No studies on aging exist, but Methadone assume increased potency in Assume 50% reduction elderly Toxic metabolite normeperidine, Use only for postoperative Meperidine Do not use whose renal excretion decreases with shivering age Slightly greater liver metabolism than Vecuronium Slower onset ( 33%) Slower recovery times renal, age nearly doubles metabolic t½ Liver metabolism slightly greater than Rocuronium Minimally slower onset renal, modest increase in metabolic t½ by age Succinylcholine Slower onset ( 40%) Despite pharmacokinetic General anesthesia inhaled agents 6% change per decade of age -> age adjusted MAC Anesth Analg. 2015 Sep;121(3):645-51 propofol Decreased protein binding Higher free, unbound plasma drug levels Decreased volume of distribution Slower redistribution of drug marked sensitivity to propofol (personal bias -I reduce dose by roughly 50%) 7

Opiates more potent & longer duration Distribution d/t body composition: increase in adipose tissue, decrease in lean body mass and decrease in total body water. Reduction in hepatic blood flow and volume (metabolism) Impaired Phase I reactions : oxidation, hydroxylation, and dealkylation Reductions in renal blood flow and glomerular filtration rate ( clearance of morphine and hydromorphone) Meperidine? Benzodiazepines? 8

Neuromuscular blocking agents Water soluble (not fat soluble) BUT Beware of residual paralysis!!! (-> hypoxemia, hypercarbia, agitation, hypothermia). Anesthesiology. 2015 Dec;123(6):1322-36. Chemical prophylaxis of delirium? How to intubate? 9

How to intubate? 76 yoman 70% burns How to intubate? S.M. H4276961 102 yo Female Hx- Breast cancer s/p Rt Mastectomy (1980s). Bladder cancer (?) Last seen by physician >1year Last 6 months- weaker and probably lost weight. Rx Furosamide, Potasium, Senna, Multivitamin. Lives in assisted living facility, ambulates with walker, help with ADLs. Enjoys good food, reading the New Yorker and talking politics. 10

Questions? itayb@uw.edu 11