2012-­‐046/2012 Sep Hypertension peri opera5ve treatment J P Mulier More info www.publica5onslist.com/
jan.mulier Mulier Jan 2014 1 Is Peri Opera5ve Hypertension a frequent problem? •  Peri opera5ve hypertension occurs in 25% of of hypertensive pa5ents that undergo surgery. –  Prys-­‐Roberts 1971 –  Goldman, Caldera 1979 2012-­‐046/2012 Sep •  During surgery, all pa5ents (with and without preexis5ng hypertension) are likely to develop hypertension and tachycardia. (insufficient anesthesia, stress response not blocked!) –  Erstad, Barle[a 2000 •  S5ll a problem today? With be[er hypno5cs, opioids, opioid free..? •  Need to delay anesthesia? Mulier Jan 2014 2 Components of general anaesthesia 1.  Unconsciousness –
Basal nuclei & cerebral cortex 2.  Immobility –
Brain stem & Spinal cord & neuromuscular junc5on 3.  Control of Autonomic reflexes vagal-­‐sympathe5c –
Avoid reac5on to surgical, anaesthe5c, pain s5muli 4.  Reversibility 5.  Amnesia? 6.
Analgesia (pain)?
2012-­‐046/2012 Sep –
-­‐ Irrelevant when you’re unconscious -­‐ Irrelevant when you’re unconscious There is NO PAIN percep5on, only nocicep5ve s5mula5on when you’re unconscious. (resul5ng in sympathe5c response) 7.  Hormonal stress response comparable to sympathe5c reac5on –
Suppress to limit organ damage 8.  Suppression of Inflammatory response –
Avoid over-­‐reac5on with oedema, organ dysfunc5on and fibrosis. 9.  Control of Immunologic response –
Avoid suppression to keep defence against infec5on, neoplas5c cells Mulier Jan 2014 3 Blood pressure during anaesthesia •  Sympathe5c ac5va5on rises blood pressure –  by 30 mmHg and HR by 20 b/min in normotensive pt. –  by 90 mmHg and HR by 40 b/min in untreated hypertensionpt. •  Wolfsthal Is blood pressure control necessary before surgery? Med Clin North Am. 1993; 77: 349 •  The MAP tends to fall as anaesthesia progresses: –  direct effects of the anaesthe5c, inhibi5on of the sympathe5c nervous system, and loss of the baroreceptor reflex control of arterial pressure. 2012-­‐046/2012 Sep •  This results in episodes of intraopera5ve hypotension. –  Hypertensive pa5ents experience more intraopera5ve unstable blood pressure (hypotension or hypertension) •  Blood pressure and HR slowly increase as pa5ents recover from the effects of anaesthesia. –  Hypertensive pa5ents experience more hypertension when awakening, shivering, pain. Mulier Jan 2014 4 Anesthe5c related mortality declined Bainbridge The Lancet 2012, 380: 1075 2012-­‐046/2012 Sep •  0,001 % dead rate ( 1 / 100 000) Mulier Jan 2014 5 Pearse Mortality aker surgery in Europe. The Lancet 2012, 380: 1059 60 day Mortality 4 % with 75% not admi[ed to ICU. Belgie : in hospital mort 3,2% 3.200/100.000 Nederland 2% Duitsland 2,5 % 2012-­‐046/2012 Sep •
•
•
•
•
But total peri op mortality remained high Mulier Jan 2014 6 Anesthesia should focus on total 60 days mortality instead of improving further its own safety only. 60 days peri opera5ve Health care Surgery Anesthesia 2012-­‐046/2012 Sep Is surgery more dangerous? Should we focus on morbidity? Mulier Jan 2014 7 Hypertension and Surgery •  Hypertension was the second most common risk factor for surgical morbidity. –  Khuri SF. The Na5onal Veterans Administra5on Surgical Risk Study in 83.000 pt: risk adjustment for the compara5ve assessment of the quality of surgical care. J Am Coll Surg 1995;180:519-­‐31 •  The associa5on between chronic hypertension and increased periopera5ve complica5ons 2012-­‐046/2012 Sep –  because hypertension increases the risk of cardiovascular, cerebrovascular, and renal disease, and that these comorbidi5es increase the risk of surgery. [14-­‐22]. •  It is not clear, that increased blood pressure (BP) per se increases surgical risk or that normaliza5on of BP preopera5vely reduces these risks. •  Overzealous BP control may result in unnecessary postponements of elec5ve surgery and increase the risk of ischemic organ injury and adverse drug reac5ons. Mulier Jan 2014 8 2012-­‐046/2012 Sep Hypertension: delay surgery? •  •  Op5mal •  Normal •  High normal
•  •  Hypertension
•  Stage 1 •  Stage 2 •  Stage 3 •  Stage 4 SAP <120 120–129
130–139
DAP <80 80–84 85–89 delay surgery -­‐ -­‐ -­‐ 140–159
160–179
180–209
≥210 90–99 100–109
110–119
≥120 never no – yes ? yes – no ? always Mulier Jan 2014 9 Cancella5on Survery Dix B J A 2001, 86: 789 •  4 and 28% of pa5ents presen5ng for surgery have hypertension. •  Hypertension most important factor to delay surgery. –  Morrisey. Why are opera5ons cancelled? BMJ 1989; 299: 77 •  Hypertension increases peri opera5ve complica5ons. 2012-­‐046/2012 Sep –  Howell. Risk factors for cardiovascular death aker elec5ve surgery under general anaesthesia. Br J Anaesth 1998; 80: 14 •  Systolic hypertension more risk for peri opera5ve CV morbidity than diastolic hypertension •  Trea5ng systolic hypertension reduces risk in elderly –  Wolfsthal. Is blood pressure control necessary before surgery? Med Clin North Am 1993; 77: 349 Mulier Jan 2014 10 Hypertensie Peri opera5ef behandelen? •  Graad 1: milde hypertensie -­‐> niet uitstellen maar iv behandelen –  SAP > 140 en DAP > 90 •  Graad 2: erns5ge hypertensie -­‐> niet uitstellen maar iv behandelen –  SAP > 160 en DAP > 100 •  Graad 3: ongecontroleerde hypertensie -­‐> ingreep uitstellen en po behandelen 2012-­‐046/2012 Sep –  SAP > 180 en DAP > 110 •  Outcome slechter? niet stabiele BD is slechter! •  Risico op bloeding, harvalen, weefselperfusie •  Meer POCD (post opera5ve cogni5ve dysfunc5on) •  1. Neurocogni5ve Performance in Hypertensive Pa5ents aker Spine Surgery; Anesthesiology 2009; 110:254 Mulier Jan 2014 11 Is there a difference between opioid and opioid free anesthesia? •  Both induce sympathe5c block with bradycardia and hypotension –  The speed of this effect is dependent on drug and dose. •  Remifentanyl > Sufentanyl > Fentanyl >> dexmedetomidine >> clonidine –  The dura5on is opposite to the speed of induc5on –  The drop is dependent on the dose and the drug. 2012-­‐046/2012 Sep •  If insufficient hypertension and tachycardia. –  Extra dose of remifentanyl is possible, for alpha agonists too late. •  Alpha agonist first induce hypertension, before hypotension, requiring a slow load up. •  Risk of rebound hypertension aker stopping long term treatment. Mulier Jan 2014 12 Today paradigm shik to OFA? OFA: Inhalation/propofol
local anesthetics iv,
B blockers
and non opioid analgetics,
alpha agonists,
ketamine
1. hypnosis 2012-­‐046/2012 Sep Unconsciousness Hemodynamic stability Immobility (rela<ve) 2. Autonomic reflex control 3. relaxa5on No analgesia is needed during anesthesia We need sympathe5c stability to avoid organ dysfunc5on or damage Mulier Jan 2014 13 Personal experience •  2008 (self) Hypnosis without any medica5on. 2012-­‐046/2012 Sep –  Perfect sympathe5c block without pain is possible •  Early 2011 Clonidine 300 ug, ketamine 25 mg, metoprolaat 5 mg added to 10 ug Sufentanyl. •  Mid 2011 Clonidine 150 ug, ket 12 mg, lidocaine 1 mg/kg, esmolol infusion and no sufentanyl, 1,5 MAC inhala5on. •  March 2012 Dexmedetomidine, ketamine, lidocaine 1,5 -­‐3 mg/kg, and infusion with 0,7 MAC inhala5on. •  Mid 2012 adding Mg Sulfate, bolus and ctu infusion •  Early 2013 adding dexamethasone, procaine instead of lidocaine, fluid restric5on. •  2013 90 % of my anesthesias today are OFA, 10 % opioid sparing; TIVA excep5onal. Mulier Jan 2014 14 Good indica5ons for OFA •  Obese pa5ents, pa5ents with obstruc5ve sleep apnea syndrome (OSAS) •  Asthma, COPD and other pulmonary diseases. •  Acute and chronic opioid addic5on. –  Sufficient analgesia preferen5al with non-­‐opioids is essen5al also in long-­‐
term abs5nence to avoid relapses. –  Huxtable 2011, Bryson 2010, Rundshagen 2010, Jage 2006, Stromer 2013 •  If heroine addict: subs5tu5on •  If alcohol: use clonidine/benzo •  If cocaine, amphetamines: avoid stress and craving •  Allergy, anaphylaxis for opioids? Histamine release. –  Fentanyl-­‐associated anaphylaxis (Fischer 1991,, Baldo Anaesth Intensive Care 2012; 2012-­‐046/2012 Sep 40: 216) •  Hyperalgesia problems. Is frequent but you have to ask. •  Complex regional pain syndromes (CRPS) –  Causalgia, Suddeck’s atrophy, Raynaud syndrome and reflex sympathe5c dystrophy. •  Oncologic surgery? –  Being pain free and stress free more important than immunosupression by morphine? Pro –contra opoids. •  Imani B Morphine use in cancer urgery Mulier Jsan 2014 Front pharmacol 2011; 2: 46 15 Contra indica5ons for OFA •  Absolute CI
–  Allergy to one of the drugs.?, heart block, shock, extreme
bradycardia
•  Relative CI
–  Acute Ischemic problems due to coronary stenosis?
•  Add nicardipine to give Coronary vasodilation
•  Slower loading of dexmedetomidine to avoid hypertension and
vasoconstriction.
–  Controlled hypotension with need for dry surgical field by
a low cardiac output.
2012-­‐046/2012 Sep •  Add more beta blockers, Mgsulfate
–  Sympathetic dysfunctional syndromes with orthostatic
hypotension.
•  Use less dexmedetomidine
–  Very old patients
•  Use lower dose dex
Mulier Jan 2014 16 Prac5cal OFA Protocol Sint Jan Brugge •  Pro-­‐caine 0,1 % infusion start at 1 ml/kg IBW h ( max 3 – 6 mg/kg IBW h) –  Add Ketamine 50 mg; Mgsulf 5 gr ; Ketamine 50 mg in infusion bag •  Dexamethasone 10 mg iv before induc5e, droperidol 1,25 mg iv •  Dexmedetomidine 0,5 -­‐ 1 ug/kg slow loading ( bolus of 10 20 ug) followed by 0,5 ug/kg h if > 1 hour •  Lidocaine 1,5 mg/kg loading ( procaine to slow running mas 3 mg/kg h) 2012-­‐046/2012 Sep •  Propofol 200 mg followed by inhala5on anesthesia at 0,6 – 0,8 MAC with BIS around 40%. •  Rocuronium 0,6 – 1 mg/kg IBW followed by infusion 0,6 (0,3 if Mg) mg/kg IBW/h and based on TOF PTC (if NMB is needed). •  MgSulfate loading 2,5 gr ( aker curare strong poten5alisa5on) •  Have metoprolate and nicardipine available when tachycard or hypertensive. •  Wound infiltra5on with local anesthe5cs, reduce total dose! Mulier Jan 2014 17 I Pre opera5ve hypertension •  Pre op hypertension is associated with periop tachycardia, bradycardia, hypertension –  Forrest 1992 •  Pre op hypertension increases risk for post op death 3,8 5mes –  Browner 1992 •  Cardiac death (30 d post op) is 4 5mes more likely in hypertensive pa5ents 2012-­‐046/2012 Sep –  Howell 1996 •  Postponement is recommended 5ll tension is adequately controlled, but no surgery delay if DAP < 110 –  Wolfsthal 1993 Mulier Jan 2014 18 II Intra opera5ve hypertension •  Chronically hypertensive pa5ents are more likely to experience intraopera5vely labile hemodynamics (fluctua5ons in MAP greater than 20%). –  Prys-­‐Roberts C. Studies of anesthesia in rela5on to hypertension. I. Cardiovascular responses of treated and untreated pa5ents. Br J Anaesth 1971;43:122-­‐37 2012-­‐046/2012 Sep •  Cardiac complica5ons are more likely in the presence of intraopera5ve hemodynamic instability. –  Charlson ME. Intraopera5ve blood pressure. What pa[erns iden5fy pa5ents at risk for postopera5ve complica5ons? Ann Surg 1990;212:567-­‐80. •  Achieving hemodynamic stability is more important than targe5ng an arbitrary BP. Extra iv fluids with arterial vasodila2on reduce lability. Mulier Jan 2014 19 III APH (Acute Post opera5ve hypertension) •  APH usually develops within two hours of surgery and resolves within a few hours. •  APH increases –  bleeding at the surgical site –  compromises vascular anastomoses. –  intracranial hemorrhage aker craniotomy. 2012-­‐046/2012 Sep •  APH increases risk for –  myocardial ischemia and infarc5on, cardiac arrhythmia, conges5ve heart failure with pulmonary edema as well as hemorrhagic stroke, cerebral ischemia and encephalopathy. Mulier Jan 2014 20 Reasons for APH •  Intravascular volume deple5on, anxiety, pain, anesthesia emergence, hypoxemia, hypercarbia, and bladder distension, hypothermia and shivering, drug side effects, underlying hypertension, and vascular disease. •  Type and dura5on of surgery as well as anesthe5c technique and agents used influence the development of APH. 2012-­‐046/2012 Sep •  Clonidine/dexmedetomidine withdrawal syndrome •  Ac5va5on of the sympathe5c nervous and renin-­‐ angiotensin systems is a fundamental component of APH •  Increase in akerload with an increase in SBP and DBP with or without tachycardia. Mulier Jan 2014 21 Clonidine/dex withdrawal syndrome •  Occurs 18 to 24 hours aker abruptly stop taking clonidine. •  Occurs 4 to 6 hours aker stopping dexmedetomidine •  Excessive sympathe5c ac5vity with rebound hypertension, –  this syndrome resembles the pheochromocytoma. •  It may be aggravated by a beta blocker (which blocks peripheral 2012-­‐046/2012 Sep vasodilatory beta-­‐receptors, leaving vasoconstric5ng alpha receptors unopposed). •  Dexmedetomidine, alleviates withdrawal syndrome following use of cocaine, opioids, and benzodiazepines, and it may have u5lity in pa5ents with clonidine withdrawal syndrome •  Clonidine/dex withdrawal syndrome can be prevented by adding low dose clonidine post opera5ve. (75 ug/12h) Mulier Jan 2014 22 2012-­‐046/2012 Sep Geen nood aan an5hypertensiva peri opera5ef? Want… 1.  We geven an5 hypertensiva verder tot op dag van opera5e samen met de premedica5e 2.  Voldoende seda5e met premedica5e en induc5e bolus lidocaine voorkomt intuba5e stress 3.  Hoge dosis opiaten voorkomt tachycardie/hypertensie en ideaal voor gecontroleerde hypotensie 4.  Hypnose verdiepen met inhala5e/Propofol geek vasodilata5e 5.  Epidurale/spinale geek vasodilata5e OL met voldoende tensie daling 6.  Goede pijnverdoving post opera5ef voorkomt hyperten5e Mulier Jan 2014 23 Of juist wel? Omdat… 1.  An5hypertensiva pre op niet verder geven bij ACE-­‐I en ARB (angiotensine II receptor antagonist). 2.  Premedica5e (seda5e) is te vermijden (OSAS,) 3.  Bij induc5e duurt het te lang vooraleer sufenta ac5ef is. 4.  Hoge dosis opiaten zijn te vermijden 2012-­‐046/2012 Sep 1.
Maar opiaat vrij met dexmedetomidine geek korte hypertensie 5.  Diepe hypnose met lage BIS is te vermijden 6.  Lumbale Epidurale vasodilata5e/hypotensie geek reflectoir cardiale vasoconstric5e en hart ischemie 7.  Extra iv fluids geven meer oedeem thv inflamma5e 8.  ECT met zo weinig mogelijk propofol en toch symp stress blokkeren. Mulier Jan 2014 24 Hoe bloeddruk verlagen per opera5ef? Direct via •  Vasodilata5e (arterieel) Rydene Ebran5l •  Hartdebiet dalen –  Inotropie verlagen –  Preload verlagen Seloken Cedocard •  (veneuse vasodilata5e) •  Vulling verlagen •  PEEP en ven5la5e –  Harvrequen5e vertragen Seloken 2012-­‐046/2012 Sep Indirect via •  Sympa5sche blockade Catapressan Dexdor •  Sympa5sche s5mulus verlagen –
–
–
–
Hypnose middelen Propofol Sevoflurane Opiaten en analge5ca sufentanil remifentanyl Hyperven5la5e tot hypocapnie geek hartdebiet daling Locoregionale anesth Vasodilata5e, bradycardie, neg inotropie Keuze bepaald door indica5e Mulier Jan 2014 25 2012-­‐046/2012 Sep Clinical comparison of frequently used pure vasodilators Mulier Jan 2014 Poelaert and Roosens. Acta Anaesthesiol Scand 2000; 44: 528–535 26 Veiligste bloeddruk daling •  Bloeddruk daling met hartdebiet s5jging –  Cerebrale perfusie stabiel, geen orgaan dysfunc5e •  Dus Arteriolaire vasodilata5e –  zonder bradycardie, neg inotropie of vullingsdaling 2012-­‐046/2012 Sep •  Betekent hartdebiet s5jging en betere weefselperfusie en zuurstof aanvoer •  Intraveneus preparaat •  Snel en kort werkend •  Gemakkelijk doseren en consistent voorspelbaar antwoord •  Wie voldoet hieraan? •  Ca entry blockers (Nicardipine iv) Mulier Jan 2014 27 Welk iv an5hypertensivum zou jij kiezen? (beperkt iv aanbod) •  B blocker via bradycardie, neg inotropie –  Seloken (metoprolaat), brevibloc (esmolol) •  α 1 + B blocker via brady, neg inotropie en vasodilata5e –  Trandate (labetolol) •  α2 agonisten via Sympha5cusblock –  Catapressan (clonidine) Dexdor (dexmedetomidine) •  Centrale sympathicusblock en zwakke α 1 blocker –  Ebran5l (urapidil) 2012-­‐046/2012 Sep •  Ca antagonisten art vasodilata5e met CO s5jging –  Rydene (nicardipine), Nimotop, Isop5ne (verapamil) •  Nitraten veneuse vasodilata5e met prelaod daling –  Cedocard, Mgsulfate •  Niet direct werkende zoals hypno5ca, locale anesthe5ca iv, analge5ca, opioiden. Mulier Jan 2014 28 Nicardipine pharmacology •  Nicardipine is more water soluble than nifedipine -­‐> IV injec5on •  Selec5vity for arterial and cardiac arterial vascular smooth muscle rela5vely large and rapid changes in BP, with minimal inotropic changes in cardiac func5on (secondary to baroreflex-­‐
2012-­‐046/2012 Sep induced adrenergic s5mula5on?) •  Cmax occurred 1 minute aker administra5on IV bolus nicardipine •  Nicardipine metabolism occurs primarily in the liver through the cytochrome P450 •  plasma concentra5ons decline: –  ini5al elimina5on (α) (t1/2α 2.7 minutes), –  intermediate elimina5on (β) half-­‐life (t1/2β 44.8 minutes) –  slow terminal elimina5on (γ) half-­‐life (t1/2γ 14.4 hours). Mulier Jan 2014 29 2012-­‐046/2012 Sep Mulier Jan 2014 30 Nicardipine effects •  Reduced influx of Ca in cardiac and smooth muscle cell –  Arterial vasodila5on with drop in Systemic vascular resistance •  Drop in SAP MAP DAP 2012-­‐046/2012 Sep –  An5spas5c effect on coronary artery, cerebral artery –  Minimal venodilatory effects •  HR increase secondary to reflex sympathe5c ac5va5on •  Cardiac output increase, coronary blood flow increase, cerebral blood flow increase without ICP increase •  No drop in uterus flow Mulier Jan 2014 31 Indica5es voor peri opera5eve an5 hypertensiva 1.
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3.
2012-­‐046/2012 Sep 4.
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Preven5e van stress reac5e op –  Anesthesie Induc5e, extuba5e, chirurgische s5mulus, ECT Hypertensie opstoot –  Essen5ele Hypertensie, Isolated Systolic Hypertension –  Pheochromocytoom –  Pre eclampsie Gecontroleerde hypoten5e –  bloedleeg op veld: veneus, art, cappillair –  Bloedverlies beperken Akerload reduc5e: –  Harvalen met onvoldoende CO Vaso spasm preven5on, treatment –  Cerebraal –  Raynaud –  Coronairen Mulier Jan 2014 32 Indica5es voor peri opera5eve an5 hypertensiva 1.
Preven5e van stress reac5e per opera5ef –  Anesth Induc5e, chirurgische s5mulus, ECT symp stress, extuba5e •  Klassiek hoge dosis opiaten –  Maar fenta, sufenta duurt > 5 min vooraleer effect. –  Remifentanyl ideaal indien opioid anesthesie •  Best sympathicus block met dexmedetomidine –  Al5jd te laat! duurt 10 min vooraleer effect. •  Lidocaine iv 1,5 mg/kg. –  Sneller dan suf maar effect niet zo sterk. 2012-­‐046/2012 Sep •  Propofol 3 mg/kg bolus vasodilata5e en hartdebiet daling –  1 mg/kg bij ECT niet voldoende, beter B blocker of alpha blocker associeren die geen Epilepsie suppressie geven. •  B blockers ? Hartdebiet daling ! –  Ideaal indien hyperten5e met tachycardie. •  Mg sulf 2,5 g (40 mg/kg) Vasodila5e & hartdebiet daling. •  Nicardipine 2 -­‐5 mg bolus of infuus: Snelst geen daling hartdebiet. –  Ideaal zo hyperten5e zonder tachycardie. Mulier Jan 2014 33 2012-­‐046/2012 Sep •  2000 Charuluxananan Nicardipine versus lidocaine for a[enua5ng the cardiovascular reponse to intuba5on. J Anesth 2000; 14: 77 Mulier Jan 2014 34 Nicardipine 30 ug/kg versus 1,5 mg/kg Esmolol •  Kovac A Comparison of nicardipine verus esmolol in a[enua5ng the hemodynamic responses to anesthesia emergence and extuba5on. J 2012-­‐046/2012 Sep cardiothoracic and vascular anesthesia 2007; 21: 45 Mulier Jan 2014 35 0,5 – 1 mg/kg Esmolol + 15 – 30 ug/kg Nicardipine •  Best: 1 mg/kg esmolol + 30 ug/kg nicardipine 2012-­‐046/2012 Sep •  2002 Tan H. Combined use of esmolol and nicardipine to blunt the haemodynamic changes following laryngoscopy and tracheal intuba5on Anesthesia 2002; 57: 1195 Mulier Jan 2014 36 Three ca-­‐entry blockers 2012-­‐046/2012 Sep •  Mikawa B J Comparison of nicardipine (rydene), dil5azem (5ldiem) and verapamil (isop5ne) for controlling the cardiovascualr responses to tracheal intuba5on. Anesthesia 1996; 76: 221 Mulier Jan 2014 37 2012-­‐046/2012 Sep Mulier Jan 2014 38 2012-­‐046/2012 Sep Mulier Jan 2014 39 Labetolol 0,4 mg/kg vs Nicardipine 20 ug/kg •  Ryu J. Compara5ve Prophylac5c and Therapeu5c Effects of Intravenous Labetalol 0.4 mg/kg and Nicardipine 20 ug/kg on Hypertensive Responses to Endotracheal Intuba5on in Pa5ents Undergoing Elec5ve Surgeries With General Anesthesia: A Prospec5ve, Randomized, Double-­‐Blind Study Clin 2012-­‐046/2012 Sep Ther. 2012;34:593 Mulier Jan 2014 40 2012-­‐046/2012 Sep Mulier Jan 2014 41 Labetolol 0,4 mg/kg vs Nicardipine 20 ug/kg •  Ryu J. Compara5ve Prophylac5c and Therapeu5c Effects of Intravenous Labetalol 0.4 mg/kg and Nicardipine 20 ug/kg on Hypertensive Responses to Endotracheal Intuba5on in Pa5ents Undergoing Elec5ve Surgeries With General Anesthesia: A Prospec5ve, Randomized, Double-­‐Blind Study Clin 2012-­‐046/2012 Sep Ther. 2012;34:593 Mulier Jan 2014 42 Nicardipine 20 ug/kg + 0 -­‐ 0,25 – 0,5 – 1 mg/kg esmolol •  Moon Y. The op5mal dose of esmolol and nicardipine for maintaining cardiovascular stability during rapid-­‐sequence induc5on Journal of 2012-­‐046/2012 Sep Clinical Anesthesia 2012; 24: 8 Mulier Jan 2014 43 Indica5es voor peri opera5eve an5 hypertensiva 1.
Preven5e van stress reac5e per opera5ef 2.  Hypertensie opstoot –  Essen5ele Hypertensie, Isolated Systolic Hypertension •  Verder ze[en an5 hypertensie med preop (uitz ACE inhib; ARB) •  Acute perop opstoot: Nicardipine iv 2012-­‐046/2012 Sep –  Pheochromocytoom •  B blokkers, α blokker en Ca entry blokker voor perop opstoot •  Esmolol, (Fentolamine, Prazosine alleen po), Nicardipine –  Pre eclampsie •  Ca entry blocker Nicardipine iv Mulier Jan 2014 44 pheocromocytoom 2012-­‐046/2012 Sep •  Vooraf sterk a en B blockade. •  Ideaal als bijkomend middel per opera5ef om opstoot op te vangen. •  Geen cardiale depressie Mulier Jan 2014 45 Pre eclampsie 2012-­‐046/2012 Sep •  Preferen5al spinal anesthesia •  If clo}ng problems general A: TIVA •  Mg sulf, labetolol or nicardipine (less transplacentair) –  Nicardipine is a very effec5ve therapy for treatment of severe hypertension in pregnancy and may be a be[er alterna5ve to other available treatment op5ons •  Nij Bijvank SW, Nicardipine for the treatment of severe hypertension in pregnancy: a review of the literature. Obstet Gynecol Surv. 2010;65:341 Mulier Jan 2014 46 Indica5es voor peri opera5eve an5 hypertensiva 1.
2.
Preven5e van stress reac5e op Hypertensie opstoot 3.  “Gecontroleerde” hypoten5e = ongecontroleerd (tenzij CO me5ng: Nexfin ideaal maar welk CO is voldoende laag?) –  Bloedverlies beperken of bloedleeg opera5e veld: 2012-­‐046/2012 Sep •  Veneus: fluids beperken, lage CVD: lever chirurgie •  Art: vasodilata5e, hoog CO en lage BD: vaatchirurgie –  Rydene (nicardipine) •  Capillair: laag CO: mandibular osteotomy, tympanoplasty, endoscopic sinus, nasal surgery, … –  Direct Sympha5cus block – indirect (nadeel vasodilata5e) –  Vasoconstrictoren: niet zinvol bij faciale chirurgie omdat dit bed niet reageert Mulier Jan 2014 47 Controlled hypotension reduced blood loss •
blood loss with 50% when MAP was decreased to 55–65mm Hg –
•
blood loss by half (from 304mL to 186mL) in mandibular osteotomy. –
•
Hersey SL. Nicardipine versus sodium nitroprusside for controlled hypotension during spinal surgery in adolescents. Anesth Analg 1997; 84: 1239-­‐44 blood loss from 1800mL to 1000mL in prosthe5c surgery of the knee with a tourniquet. –
•
Enlund M. Cerebral normoxia in the rhesus monkey during isoflurane-­‐ or propofol-­‐induced hypotension and hypocapnia, despite disparate blood-­‐flow pat-­‐ terns: a positron emission tomography study. Acta Anaesthesi-­‐ ol Scand 1997; 41: 1002-­‐10 blood loss by half (from 1297mL to 761mL) in paediatric spinal surgery. –
•
Eckenhoff JE, Rich JC. Clinical experiences with deliberate hypotension. Anesth Analg 1966; 45: 21-­‐8 Juelsgaard P. Hypotensive epidural anesthesia in total knee replacement without tourni-­‐ quet: reduced blood loss and transfusion. Reg Anesth Pain Med 2001; 26: 105-­‐10 blood loss from 667 to 480mL and from 263 to 179mL in surgery of the hip. Yukioka H, Prostaglandin E1 as a hypotensive drug during general anesthesia for total hip re-­‐ placement. J Clin Anesth 1993; 5: 310-­‐4 –  Sharrock NE, The effect of two levels of hypotension on intraopera5ve blood loss during total hip arthroplasty performed under lumbar epidural anesthesia. Anesth Analg 1993; 76: 580-­‐4 2012-­‐046/2012 Sep –
•
transfusion from 2.7 to 1.3 units of blood cells and blood loss from 1000 to 600mL in total hip replacement surgery. Karakaya D, Acute normovolemic hemodilu5on and nitroglycerin-­‐induced hypotension: compar-­‐ a5ve effects on 5ssue oxygena5on and allogeneic blood trans-­‐ fusion requirement in total hip arthroplasty. J Clin Anesth 1999; 11: 368-­‐74 –  Niemi TT, Comparison of hypo-­‐ tensive epidural anaesthesia and spinal anaesthesia on blood loss and coagula5on during and aker total hip arthroplasty. Acta Anaesthesiol Scand 2000; 44: 457-­‐64 –
•
blood loss from 1920 to 1260mL and from 1335 to 788mL in radical prostatectomy. Boldt J, Acute normovolaemic haemodilu5on vs controlled hypotension for reducing the use of allogeneic blood in pa5ents undergoing radical prostatectomy. Br J Anaesth 1999; 82: 170-­‐4 –  Su[ner SW, Cerebral effects and blood sparing efficiency Mulier Jan 2014 of sodium sodium nitroprusside-­‐induced hypotension 48 alone and in combina5on with acute normovolaemic haemodilu5on. Br J Anaesth 2001; 87: 699-­‐705 –
2012-­‐046/2012 Sep Mulier Jan 2014 49 Capacity to Improve the Quality of the Opera5ve Field •  Only a few studies –  difficulty in finding objec5ve criteria apart from the visual approach. •  The reduc5on in MAP from 90mm Hg to 50–65mm Hg or in SBP from 125mm Hg to 70–90mm Hg during –  endoscopic sinus surgery. Esmolol superior vs nitroprusside •  Boezaart AP. Comparison of sodium sodium nitroprusside-­‐ and esmolol-­‐induced controlled hypotension for func5onal endoscopic sinus surgery. Can J Anaesth 1995; 42: 373-­‐6 –  mandibular osteotomy no diff nitroglycerine vs isoflurane •  Schindler I. Moderate induced hypotension provides sa5sfactory opera5ng condi5ons in maxillofacial surgery. Acta Anaesthesiol Scand 1994; 38: 384-­‐7 2012-­‐046/2012 Sep –  tympanoplasty[2,7-­‐10] remifentanyl-­‐propofol vs nitroprusside-­‐alf-­‐prop vs esmolol-­‐
alf-­‐prop •  Marchal JM. Clonidine decreases intraopera5ve bleeding in middle ear microsurgery. Acta Anaesthesiol Scand 2001; 45: 627-­‐33 •  Degoute CS. Remifentanil and controlled hypotension; comparison with sodium nitroprusside or esmolol during tympanoplasty. Can J Anesth 2001 Jan; 48 (1): 20-­‐7 provided a good opera5ng field. Mulier Jan 2014 50 2012-­‐046/2012 Sep Mulier Jan 2014 51 2012-­‐046/2012 Sep Mulier Jan 2014 52 2012-­‐046/2012 Sep Mulier Jan 2014 53 2012-­‐046/2012 Sep Mulier Jan 2014 54 Gecontroleerde hypotensie om capillaire bloeding te beperken •  Hoge dosis opiaten via TIVA: sympha5cus block –  Remifentanyl propofol: CO daling met weefselperfusie daling en dus minder capillaire weefsel bloedingen •  Hoge dosis B blockers?: Esmolol, (bij hypertensie 2012-­‐046/2012 Sep +Ca entry blockers:Rydene; bij hypotensie +vasoconstrictoren: phenylephrine) •  Hoge dosis α2 agonisten? Dexdor ( extra B blocker om CO daling nodig, (Ca entry blocker?) •  Nooit inhala5e of ca entry blockers alleen: vasodilata5e en CO s5jging! Mulier Jan 2014 55 Indica5es voor peri opera5ve an5 hypertensiva 1.
2.
3.
Preven5e van stress reac5e op Hypertensie opstoot Gecontroleerde hypoten5e 4.  Akerload reduc5e: –  Harvalen met onvoldoende CO •  Cedocard alleen preload •  Ca entry blockers en inotropica 2012-­‐046/2012 Sep –  Nicardipine (Rydene) + Dobutamine •  Beter inodilatoren (phosfodiesterase inhibitor, Ca sensi5va5on) –  Corotrope (milrinone), Enoximone(Perfan), Levosimendan (Simdax) Mulier Jan 2014 56 2012-­‐046/2012 Sep •  double-­‐blind, randomized, self-­‐controlled, dose-­‐ranging study •  in 40 adult cardiac surgical pa5ents •  to determine the pharmacokine5cs and pharmacodynamics of nicardipine 0.25 mg, 0.50 mg, 1.00 mg, and 2.00 mg administered as an IV bolus. Mulier Jan 2014 et al. Anesth Analg 1999;89:1116–23 57 Cheung Change in SBP and DBP aker nicardipine administra5on •
•
•
2012-­‐046/2012 Sep •
•
Nicardipine selec5vely decreased arterial pressure in a dose-­‐dependent manner with a maximum response within 100 s and recovery to half the maximum response within 3–7 min without associated changes in heart rate. Mulier Jan 2014 et al. Anesth Analg 1999;89:1116–23 58 Cheung 2012-­‐046/2012 Sep Change in cardiac output aker nicardipine administra5on Mulier Jan 2014 et al. Anesth Analg 1999;89:1116–23 59 Cheung Mean plasma nicardipine aker bolus administra5on The 5me course for nicardipine bolus was consistent with a two-­‐
compartment pharmacokine5c model with rapid redistribu5on from a small central compartment. 2012-­‐046/2012 Sep •
Mulier Jan 2014 et al. Anesth Analg 1999;89:1116–23 60 Cheung 2012-­‐046/2012 Sep •  Systemic and coronary hemodynamic effects of the dihydropyridine calcium antagonist, nicardipine, were studied in 15 pa5ents. •  Nicardipine was administered as a 2-­‐mg bolus intravenously followed by an infusion 5trated to maintain a 10 to 20-­‐mm Hg decrease in systolic pressure. Mulier Lambert Jan 2014 et al. Am J Cardiol 1985;55:652-­‐656 61 Aor5c pressure, heart rate and coronary flow aker nicardipine administra5on A 2-­‐mg bolus injec5on was given over 1 min followed by an infusion. 2012-­‐046/2012 Sep •
Mulier Lambert Jan 2014 et al. Am J Cardiol 1985;55:652-­‐656 62 HR, Aor5c pressure, CO, systemic vascular resistance, coronary blood flow and coronary resistance aker nicardipine administra5on A 2-­‐mg bolus injec5on was given over 1 min followed by an infusion. 2012-­‐046/2012 Sep •
Mulier Jan 2014 63 Lambert et al. Am J Cardiol 1985;55:652-­‐656 Coronary vs systemic vascular resistance aker nicardipine administra5on Iden5ty line Nicardipine •
•
•
•
Verapamil 2012-­‐046/2012 Sep Nifedipine Verapamil •
•
•
Broken line: iden5ty Large filled circle: individual pa5ent data Small filled circle with bars: mean data Open circle: mean data for nifedipine Open square: mean data for verapamil Filled squares: mean data for verapamil with slow atrial pacing Nicardipine produced a rela<vely greater change in coronary resistance than systemic resistance. Mulier Lambert Jan 2014 et al. Am J Cardiol 1985;55:652-­‐656 64 Indica5es voor peri opera5ve an5 hypertensiva 1.
2.
3.
4.
Preven5e van stress reac5e op Hypertensie opstoot Gecontroleerde hypoten5e Akerload reduc5e 5.  Vaso spasm prev, treat: Ca entry blockers ideaal –  Cerebraal: preven5e ischemische letsels bij subarachnoidale bloeding 2012-­‐046/2012 Sep •  Nimodipine (Nimotop) ctu infuus –  Perifeer: syndr Raynaud •  Nifedipine po of nicardipine iv (+ dexmedetomidine? Te traag!) –  Coronair:
stabiele en vasospas5sche angor •  Nicardipine (rydene)
Mulier Jan 2014 65 Key points to remember •  Snel symp hyperten5e reac5e blokkeren met –  nicardipine indien bradycard –  B blocker indien tachycard •  BD opstoot pheo -­‐ eclampsie – essen5ele hypert 2012-­‐046/2012 Sep –  Nicardipine (ev associeren met B blocker) •  Nicardipine niet eerst keus bij gecontroleerde hypotensie •  Akerload reduc5e bij cardiac falen –  Nicardipine + dobut of beter inodilator •  Nicardipine ideaal voor snelle vasospasme behandeling Mulier Jan 2014 66 2012-­‐046/2012 Sep Mulier Jan 2014 67 2012-­‐046/2012 Sep Geleidelijk effect gewenst: meestal op intensieve Mulier Jan 2014 68 Onmidellijk effect gewenst met infuus: ICU -­‐ OP 2012-­‐046/2012 Sep •  Onmiddelijk effect met bolus (per opera5ve) –  20 ug/kg of 1 tot 2 mg iv bolus –  Effect binnen 1 minuut, effect duurt niet lang (15 min) •  Tweede bolus of infuus starten aan 5 mg/h •  Na Infuus T1/2 1,4 h Mulier Jan 2014 69 Bereiding van Rydene I.V. 1 mg/ml onverdund 2012-­‐046/2012 Sep Bolus toediening per 1 mg (1 ml) •  1 ampul bevat 5 ml of 5 mg (1mg/ml) Spuitpomp: 1 mg/ml •  20 ml: 4 ampullen van Rydene 5mg/5ml •  50 ml: 10 ampullen van Rydene 5mg/5ml SPK Rydene 02/2011 Mulier Jan 2014 70 2012-­‐046/2012 Sep •  “Dihydropyridines are useful pharmacological agents with various ac5ons. •  Although nifedipine s5ll remains the prototype of the vasodila5ng CCEB, it acts abruptly and is not easily administered intravenously. (niet meer beschikbaar) •  Nicardipine is a CCEB with strong pre-­‐capillary vasodila5ng and an5-­‐
ischaemic proper5es. Its rapid onset and the low incidence of side effects are beneficial characteris5cs. •  In this way, it is to be recommended for intravenous use in the treatment of –  any (acute) arterial hypertension, –  preven5on and treatment of coronary vasospasm, –  induc5on of intraopera5ve controlled hypotension.” Mulier Jan 2014 Poelaert and Roosens. Acta Anaesthesiol Scand 2000; 44: 528–535 71 Why are opioids so successfull? •  Opioids blocks ascending nocicep5ve s5muli, –  thereby reducing the concentra5on of hypno5cs (inhaled or IV anesthe5cs) required to induce •  unconsciousness, immobility and hemodynamic stability 2012-­‐046/2012 Sep •  We have used opioids in combina5on with inhaled or iv anesthe5cs –  NOT to “treat intraopera5ve pain”, –  but to reduce the inhaled or iv anesthe5cs required to achieve our goals. –  “Mac sparing effect of opioids” •  But at high dose: “Higher chance of awareness” •  Lee M, Pain Physician 2011;14: 145 Mulier Jan 2014 72 But No nega<ve inotropic effects of opioids (except alfentanyl) 2012-­‐046/2012 Sep Effect of alfentanil, fentanyl, sufentanil, and remifentanil on maximum isometric active force
(left panel) and the peak of the positive force derivative (right panel)
Hanouz J et al. Anesth Analg 2001;93:543-549
Mulier Jan 2014 73 Why a new Paradigm today? 1.  Immuno suppression by opioids?
Wybran J. Suggestive evidence for receptors for morphine and methionine-enkephalin
on normal human blood T lymphocytes. J Immunol. 1979;123:1068-70
1992 Dr Paul Janssens invented Remifentanyl but refused to market Remifentanyl and
sold it to Beecham afraid of unknown long-lasting effects of opioids…
Sacerdote P. Non-analgesic effects of opioids: mechanisms and potential clinical
relevance of opioid-induced immunodepression. Curr Pharm Des. 2012;18(37):6034-42.
•  Morphine decreases natural and acquired immunity, both directly and indirectly via
the activation of central receptors.
2012-­‐046/2012 Sep •
•
•
the immunological effects of opioid are receiving considerable attention because of
concerns that opioid-induced changes in the immune system may affect the
outcome of surgery or of variety of disease processes, including bacterial and
viral infections and cancer.
The impact of the opioid-mediated immune effects could be particularly dangerous
in selective vulnerable populations, such as the elderly or immunocompromised patients.
Choosing anesthetic drugs without an effect on immune responses may be an
important consideration in anesthesia.
Mulier Jan 2014 74 Why a new Paradigm today? 2. Fentanyl induces fixed neurologic
sequels? (Periventricular
Leucomalacia)
2012-­‐046/2012 Sep –  Neonatal outcome and prolonged analgesia in neonates.
Anand et al. Arch Pediat Adolesc Med 1999; 153: 331-8
3. Opioids induced hyperalgesia?:
Patients receiving opioids become more
sensitive to pain.
–  Opioids are short lasting analgesics and
long-during hyperalgesics by upregulation of
compensatory pronociceptive pathways
–  Angst MS. Opioid-induced hyperalgesia: a qualitative
systematic review. Anesthesiology. 2006;104:570-87
Mulier Jan 2014 75 What do we need, peri-­‐op? Per operative we need:
•  Unconsciousness; hemodynamic stability; immobility
2012-­‐046/2012 Sep –  high dose opioids was the simplest method to keep
stable hemodynamics, to reduce hypnotics and to block
breathing
–  therefore we thought we needed analgetics and made
them the third cornerstone of anesthesia: analgesia
–  But we need to control the Autonomic reflex during surgical pain s5muli. Instead of opioids sympathe5c blockers are also usefull.
Post operative we need:
•  Analgesia, consciousness, full muscle strength:
–  low dose opioids not always enough (due to high dose
addiction per op)
•  Use PCIA PCEA … local, locoregional addition
–  avoid opioids side effects post operative: multimodal
analgetics
Mulier Jan 2014 76 How to avoid opioids? •  Direct sympathetic block central - peripheral
–  Clonidine, Dexmedetomidine, B blockers
•  Indirect block of sympathetic effects
–  Nicardipine, lidocaine, Mg sulfate, inhalation vapor
•  Multimodal analgetics (non opoids) loading up per
operative to be active when waking up.
2012-­‐046/2012 Sep –  low dose ketamine, dexmedetomidine, lidocaine,
diclofenac, paracetamol
•  Epidural, plexus and local infiltration block
•  Spinal anesthesia with higher sympathical nerve
block. Epidural block.
Mulier Jan 2014 77 Hemodynamic stability possible? 2012-­‐046/2012 Sep •
•
•
•
•
•
•
Dex Lidocaine MgSulfate Ketamine Propofol Inhala5on Opioid free preload
contrac
akerload
HR
CO MAP ? ? ? Mulier Jan 2014 78 Effect of clonidine-­‐dexmedetomidine on post-­‐op opioid use 2012-­‐046/2012 Sep •  Blaudszun G. Anesthesiology 2012 ; 116: 1312-22 Effect of
systemic alpha2 agonists on post operative morphine
consumption and pain intensity. Review and meta analysis.
Morphine post OP
VAS post OP
Mulier Jan 2014 79 Effect of ketamine on post-­‐opera5ve opioid use •
Bell RF Periopera5ve Ketamine for acute post opera5ve pain. the cochrane library 2010; 11 2012-­‐046/2012 Sep Cumulative postoperative patient-controlled
analgesia (PCA) morphine consumption.
Ketamine per op Placebo per op Visual analog scale score at mobilization during
the 48-h study.
Guillou N et al. Anesth Analg 2003;97:843-847
Mulier Jan 2014 80 2012-­‐046/2012 Sep Effect of Mgsulfate on per-­‐op opioids •  Kogler The analgesic effect of magnesium sulfate in pa5ents undergoing thoracotomyJ Acta Clin Croat. 2009;48:19-­‐26. Thoracotomy pa5ents received Fentanyl as required and 30-­‐50 mg/kg MgSO4 followed by con5nuous infusion of 500 mg/h or placebo. Fentanyl consump5on during the opera5on was significantly lower in the Mg treated group versus placebo. Mulier Jan 2014 81 Effect of lidocaine on post-­‐op opioid use •
McCarthy G. Drugs. 2010;70:1149-­‐63. Impact of intravenous lidocaine infusion on postopera<ve analgesia and recovery from surgery: a systema<c review of randomized controlled trials. •  33% reduc5on vs placebo in opioid consump5on postopera5ve. –  when the lidocaine infusion was maintained for 1 hour 2012-­‐046/2012 Sep •  83% reduc5on vs placebo in opioid consump5on postopera5ve. •
•
–  when the lidocaine infusion was maintained for 24 hours. earlier return of bowel function, allowing for earlier rehabilitation and shorter
duration of hospital stay. Duration of hospital stay was reduced by an average of
1.1 days in the lidocaine-treated patients.
intravenous lidocaine did not result in toxicity or clinically adverse events.
Mulier Jan 2014 82 Steroids revival for post op analgesia? •  Massera G. Indica5ons for steroid anesthesia. Acta Anaesthesiol. 1959;10:541-­‐9 2012-­‐046/2012 Sep •  Tiippana E. Effect of paracetamol and coxib with or without dexamethasone aker laparoscopic cholecystectomy. Acta Anaesthesiol Scand. 2008;52:673-­‐80 Dexamethasone 5 mg effec5ve to reduce PONV Dexamethasone 10 mg effec5ve to reduce post opera5ve opioids need Mulier Jan 2014 83 Conclusion •  Many studies show a reduction in opioid use per
operative and post operative if a non opioid additive
is added.
2012-­‐046/2012 Sep If these drugs are combined in a multimodal approach is
it possible to avoid all opioids per operative???
•  Marc de Kock (UCL Belgium) achieved this already
several years before Dexmedetomidine became
available in Europe using high dose clonidine –low
dose ketamine and esmolol.
Mulier Jan 2014 84 2012-­‐046/2012 Sep Case report 2005: Morbid obesity using dexmedetomidine without narco5cs •  433 kg morbidly obese patient with
obstructive sleep apnea and pulmonary
hypertension.
•  0.5 MAC inhalation. A continuous infusion of
dexmedetomidine (0.7 ug/kg/h) per operative
and a low infusion rate first postoperative
day.
•  48 mg morphine by PCA first day with dex
•  148 mg morphine by PCA second day
without dex.
Hofer R. Anesthesia for a patient with morbid obesity using dexmedetomidine without narcotics.
Mulier JCan
an 2014 J Anaesth. 2005; 52: 176-80.
85 2012-­‐046/2012 Sep OFA is not vivisec5on! Mulier Jan 2014 86 2012-­‐046/2012 Sep Start with opioid sparing anesthesia… 1.  Stop remifentanyl infusions, use only 10 ug sufentanil at induc5on. Measure anesthesia depth, blood pressure, HR; give low dose opioids before extuba5on. 2.  Add an alpha agonist (central direct sympathe5c block) –  Clonidine, 150 -­‐ 300 ug at induc5on dexmedetomidine infusion 0,5 – 1 ug/kg/h aker induc5on, 3.  Keep peripheral B blocker as escape if tachycard 4.  Indirect block of sympathe5c effects –  lidocaine bolus before induc5on, –  increase to 1,5 MAC inhala5on vapor, –  Keep Nicardipine or other vasodilator as escape 5.  Start non opioid analge5cs per opera5ve –  Low dose ketamine 10 – 20 mg, –  Diclofenac, keterolac or parecoxib –  Paracetamol, dexamethasone, droperidol (PONV?). 6.  Epidural, plexus and local infiltra5on block of pain nerves Mulier Jan 2014 87 How to monitor anesthesia depth during opioid free anesthesia? •  Ketamine given at a hypno5c dosis of 1,5 mg/kg rises the BIS value. (we give ketamine in OFA dosis of 0,25 mg/kg IBW far below an hypno5c dosis.) –  Wu CC. EEG-­‐bispectral index changes with ketamine versus thiamylal induc5on of anesthesia. Acta Anaesthesiol Sin. 2001;39:11-­‐5. 2012-­‐046/2012 Sep •  BIS values are elevated by a bolus dose of isoproterenol, ketamine, neos5gmine or sugammadex above 60 % while pa5ents have no recall. –  Dahaba AA. Effect of sugammadex or neos5gmine neuromuscular block reversal on bispectral index monitoring of propofol/remifentanil anaesthesia. Br J Anaesth. 2012 Apr;108(4):602-­‐6 –  Ma[hews R. Isoproterenol induced elevated bispectral indexes while undergoing radiofrequency abla5on. AANA J. 2006;74:193-­‐5 No risk for awareness if you keep BIS below 60% during OFA. Mulier Jan 2014 88 OFA Protocol Sint Jan Brugge •  Dexamethasone 10 mg iv before induc5e, droperidol 1,25 mg •  Ketamine 0,125 to 0,25 mg/kg followed by 0,125 to 0,25 mg/kg IBW/h •  Lidocaine 1,5 mg/kg IBW followed by 1,5 to 3 mg/kg IBW/h or Pro-­‐caine 0,1 % infusion at 3 mg/kg IBW. •  Dexmedetomidine 0,5 to 1 ug/kg IBW followed by 0,5 to 1 ug/kg IBW/h •  MgSulfate 40 mg/kg IBW followed by 10 mg/kg IBW/h 2012-­‐046/2012 Sep •  Propofol is given at 2,5 mg/kg IBW followed by inhala5on anesthesia at 0,6 – 0,8 MAC with BIS around 40%. •  Rocuronium 0,6 – 1 mg/kg IBW followed by infusion 1 mg/kg IBW/h and based on TOF PTC (if NMB is needed). •  Have metoprolate and nicardipine available when tachycard or hypertensive. (DHB 0,6 mg remain to prevent PONV) •  Wound infiltra5on with local anesthe5cs, reduce total dose. Mulier Jan 2014 89 Prac5cal OFA Protocol Sint Jan Brugge •  Pro-­‐caine 0,1 % infusion start at 1 ml/kg IBW h ( max 3 – 6 mg/kg IBW h) –  Add Ketamine 50 mg; Mgsulf 5 gr ; Ketamine 50 mg in infusion bag •  Dexamethasone 10 mg iv before induc5e, droperidol 1,25 mg iv •  Dexmedetomidine 0,5 -­‐ 1 ug/kg slow loading ( bolus of 10 20 ug) followed by 0,5 ug/kg h if > 1 hour •  Lidocaine 1,5 mg/kg loading ( procaine to slow running mas 3 mg/kg h) 2012-­‐046/2012 Sep •  Propofol 200 mg followed by inhala5on anesthesia at 0,6 – 0,8 MAC with BIS around 40%. •  Rocuronium 0,6 – 1 mg/kg IBW followed by infusion 0,6 (0,3 if Mg) mg/kg IBW/h and based on TOF PTC (if NMB is needed). •  MgSulfate loading 2,5 gr ( aker curare strong poten5alisa5on) •  Have metoprolate and nicardipine available when tachycard or hypertensive. •  Wound infiltra5on with local anesthe5cs, reduce total dose! Mulier Jan 2014 90 Post opera5ve analgesia •  non steroidal an5-­‐inflammatory agents –  Paracetamol 2 gr loading 1 gr/6h –  Diclofenac 150 mg loading, 2x75 mg/day –  Or Keterolac 40 mg loading, 3 x 10 mg/day 2012-­‐046/2012 Sep •  Local wound infiltra5on (calculate toxic dose!) •  and choice between –  give low dose morphine or –  keep infusion of sympathicoly5ca (ket dex lido Mg) at low dose without deep seda5on •  Ketamine 0,05 mg/kg/h •  Lidocaine 1 mg/kg/h •  Mgsulfate 10 mg/kg/h Mulier Jan 2014 •  Dexmedetomidine 0,1 – 0,2 ug/kg/h 91 Personal experience •  2008 (self) Hypnosis without any medica5on. 2012-­‐046/2012 Sep –  Perfect sympathe5c block without pain is possible •  Early 2011 Clonidine 300 ug, ketamine 25 mg, metoprolaat 5 mg added to 10 ug Sufentanyl. •  Mid 2011 Clonidine 150 ug, ket 12 mg, lidocaine 1 mg/kg, esmolol infusion and no sufentanyl, 1,5 MAC inhala5on. •  March 2012 Dexmedetomidine, ketamine, lidocaine 1,5 -­‐3 mg/kg, and infusion with 0,7 MAC inhala5on. •  Mid 2012 adding Mg Sulfate, bolus and ctu infusion •  Early 2013 adding dexamethasone, procaine Mulier Jan 2014 92 Example of a live case •  9:40 anesthesia induction Ketamine: 35 mg; Lidocaine: 210 mg;
Dexmedetomidine: 140 ug; Rocuronium: 158,1 mg; desflurane 0,8 MAC;
paracetamol 3 gr.
2012-­‐046/2012 Sep •
•
•
•
10:00 incision: insufflation of abdomen and APVR calculation.
11:16 start Lap Roux and Y gastric bypass procedure.
10:55 last surgical stitch: stop dex (multimodal) infusion.
11:01 TOF = 100 % BIS rose to 77% (not awake!) and stop
desflurane.
•  11:06 patient awake when called, extubation.
•  11:08 patient full awake, no pain, feels happy to hear that
operation is finished and had sufficient force to move himself
painfree in bed at 11:14.
Mulier Jan 2014 93 2012-­‐046/2012 Sep Awakening aker OFA Mulier Jan 2014 94 2012-­‐046/2012 Sep HR, Sat, NIBP, etCO2 Mulier Jan 2014 95 2012-­‐046/2012 Sep 02%, BIS, TOF, PTC, airw pres Mulier Jan 2014 96 2012-­‐046/2012 Sep Peak airway pressures in mmHg Mulier Jan 2014 97 Per-­‐opera5ve Problems •  Vasoconstric5on during induc5on (dex loading) –  Pale, white, hypertension, bradycardia –  R/ nicardipine 1 mg , wait 5ll prop/inhal is effec5ve •  Insufficient sympathe5c block –  Tachycardia, hypertension 2012-­‐046/2012 Sep –  Betablocker, more inhala5on, dex, lid extra •  Sympathe5c block to strong –  Bradycardia, hypotension –  R/ Ephedrine •  Not enough vasoconstric5on Mulier Jan 2014 98 2012-­‐046/2012 Sep Post-­‐opera5ve Problems •  Not waking up post opera5ve –  Lower dose clonidine / stop-­‐reduce dex pump earlier –  S5mulate pa5ent who will suddenly open his eyes and want to go asleep again. –  Wait 15 minutes (Dex) or several hours (Clonidine) •  Pain when wakening up –  Add morphine 5 mg iv at end surgery –  Switch from clonidine to dexmede5omidine –  Did you add keterolac or diclofenac? –  Are all mul5modal elements given sufficient? •  Bradycardia, hypotension –  No problem, accept HR 45 and SAP 90. –  Ephedrine extra Mulier Jan 2014 99 Good indica5ons for OFA •  Obese pa5ents, pa5ents with obstruc5ve sleep apnea syndrome (OSAS) •  Asthma, COPD and other pulmonary diseases. •  Acute and chronic opioid addic5on. –  Sufficient analgesia preferen5al with non-­‐opioids is essen5al also in long-­‐term abs5nence to avoid relapses. –  Huxtable 2011, Bryson 2010, Rundshagen 2010, Jage 2006, Stromer 2013 •  If heroine addict: subs5tu5on •  If alcohol: use clonidine/benzo •  If cocaine, amphetamines: avoid stress and craving •  Allergy, anaphylaxis for opioids? Histamine release. –  Fentanyl-­‐associated anaphylaxis (Fukuda 1986, Fischer 1991, Cummings 2007, Baldo B Anaesth Intensive Care 2012; 40: 216) 2012-­‐046/2012 Sep •  Hyperalgesia problems. Is frequent but you have to ask. •  Complex regional pain syndromes (CRPS) –  Causalgia, Suddeck’s atrophy, Raynaud syndrome and reflex sympathe5c dystrophy. •  Chronic Fa5gue and Immune Dysfunc5on Syndrome? –  Avoid histamine release, ponv preven5on, Mg and K extra, •  Oncologic surgery? –  Being pain free and stress free more important than immunosupression by morphine? Pro –contra opoids. •  Imani B Morphine use in cancer surgery Front pharmacol 2011; 2: 46 Mulier Jan 2014 100 Contra indica5ons for OFA •  Absolute CI
–  Allergy to one of the drugs.?, heart block, shock, extreme
bradycardia
•  Relative CI
–  Acute Ischemic problems due to coronary stenosis?
•  Add nicardipine to give Coronary vasodilation
•  Slower loading of dexmedetomidine to avoid hypertension and
vasoconstriction.
–  Controlled hypotension with need for dry surgical field by
a low cardiac output.
2012-­‐046/2012 Sep •  Add more beta blockers, Mgsulfate
–  Sympathetic dysfunctional syndromes with orthostatic
hypotension.
•  Use less dexmedetomidine
–  Very old patients
•  Use lower dose dex
Mulier Jan 2014 101 We learned that we need 1. 2. 3. Balanced anesthesia: Inhala5on, opioids, NMB TIVA: propofol, opioids, NMB 1. hypnosis 2012-­‐046/2012 Sep Unconsciousness Hemodynamic stability Immobility (rela<ve) 2. analgesia 3. relaxa5on Do we need analgesia to achieve hemodyn stability? Mulier Jan 2014 102 Today paradigm shik to OFA? OFA: Inhalation/propofol
local anesthetics iv,
B blockers
and non opioid analgetics,
alpha agonists,
ketamine
1. hypnosis 2012-­‐046/2012 Sep Unconsciousness Hemodynamic stability Immobility (rela<ve) 2. Autonomic reflex control 3. relaxa5on No analgesia is needed during anesthesia We need sympathe5c stability to avoid organ dysfunc5on or damage Mulier Jan 2014 103 Components of general anesthesia 1.  Unconsciousness 1.
Basal nuclei & cerebral cortex 1.
Brain stem & Spinal cord & neuromuscular junc5on 2.  Immobility 3.  Control of Autonomic reflex vagal-­‐sympathe5c 4.  Reversibility 5.  Amnesia? 2012-­‐046/2012 Sep 6.
1.
Irrelevant when you’re unconscious 1.
There is NO PAIN, only nocicep5ve s5mula5on when you’re unconscious. (resul5ng in sympathe5c response) Analgesia (pain)? 7.  Suppression of Hormonal stress response 8.  Control of Immunologic response 9.  Suppression of Inflammatory response Mulier Jan 2014 104 Why are inhala5on agents not sufficient? •  If MAC akinesia = 1 (no movement in 50 % of pa5ents) –  In 95 % = 1,3 Mac if 99,99% use NMB 2012-­‐046/2012 Sep •  Then MAC awake = 0,35 (unconsciousness in 50 % of pt) –  In 99,99% = 0,7 Mac •  Then MAC bar = 2 (no hemodynamic reac5on in 50 % of pt) –  In 95 % = ? Mac If 99,99 % use opioids or OFA Mulier Jan 2014 105 Start with Opioid Sparing Anesthesia (OSA) con5nue to Opioid Free Anesthesia (OFA) 2012-­‐046/2012 Sep •
•
•
•
OSA is a must for every pa5ent. OFA is possible for many pa5ents. Is an alterna5ve for opioid anesthesia! Is be[er for a selec5ve group of pa5ents!! OFA might be usefull for most pa5ents? Mulier Jan 2014 106 2012-­‐046/2012 Sep More research is needed before becoming evidence based. Try it slowly and listen to your pa5ents. Mulier Jan 2014 107