Analgesie, Sedierung und Delirmanagement – Herausforderungen bei der Analgesie und Sedierung von Neurointensivpatienten

Zusammenfassung

Die sichere und effektive Analgesie und Sedierung von Neurointensivpatienten, v.a. bei erhöhtem intrakraniellen Druck, stellt eine Herausforderung dar. Voraussetzung ist die Festlegung eines der individuellen Situation angepassten Sedierungsziels (bei intrakranieller Hypertension RASS -5) und die regelmäßige Überprüfung von Sedierungstiefe und bedarfsgerechter Analgesie mit Hilfe standardisierter Monitoring-Instrumente (z.B. RASS, ggf. unter Zuhilfenahme apparativer Verfahren, und NCS). Ausreichend evidenz-basierte Sedierungs-Algorithmen existieren in diesem Patientenkollektiv nicht. Zur kontinuierlichen Analgesie können Remifentanil, Sufentanil und Fentanyl sicher eingesetzt werden, Bolus-Gaben von Opioiden sollten vermieden werden. (S-)-Ketamin kann als Opioid-Alternative oder ergänzend bei intubierten und mit einem GABA-Rezeptor-Agonisten sedierten Patienten eingesetzt werden. Propofol und Benzodiazepine können gleichermaßen sicher und effektiv eingesetzt werden bei kürzeren Aufwachzeiten für Propofol. Barbiturate eignen sich nur zur Behandlung des therapierefraktären Status epilepticus oder der therapierefraktären intrakraniellen Hypertension. Im Hinblick auf den Einsatz von Dexmedetomidin und volatilen Anästhetika besteht noch Forschungsbedarf.

Abstract

Analgesia and sedation of patients in the neuro intensive care unit, in particular in case of intracranial hypertension, remains a challenge even today. A goal for analgesia and sedation should be set for each individual patient (RASS -5 in case of intracranial hypertension) and should be re-evaluated repeatedly based on standardized scores (RASS plus EEG monitoring where appropriate, NCS). There are no sufficient evidence-based sedation algorithms in this patient cohort. Remifentanil, sufentanil and fentanyl have been proven safe and effective for continuous application; however, bolus application should be avoided. (S-)Ketamin can be considered safe when mechanical ventilation and sedation with GABA receptor agonists are applied. Propofol and benzodiazepines are equally safe and effective with shorter wake up times for propofol. The use of barbitarutes is restricted to intractable intracranial hypertension or status epilepicus. Evidence for alpha-2-adrenoceptoragonists and inhalative sedation is poor and requires further research.

Kernaussagen

• Für den einzelnen Patienten soll ein der aktuellen Situation angepasstes Sedierungsziel festgelegt und dieses – gemeinsam mit dem Schmerzniveau – in regelmäßigen Abständen überprüft und ggf. angepasst werden.

• Für Neurointensivpatienten mit intrakranieller Hypertension gilt ein Ziel-RASS von -5 unter Vermeidung von Übersedierung (apparatives Monitoring).

• In der Neurointensivmedizin müssen die gewählten Analgetika und Sedativa den pathophysiologischen Besonderheiten von Patienten mit zerebraler Grunderkrankung angepasst werden.

• Eine kontinuierliche i. v. Gabe von Analgetika und Sedativa sollte stets unter MAP-Kontrolle erfolgen, um deletäre Effekte auf CPP und ICP zu vermeiden.

• Bolus-Gaben von Opioiden sollten vermieden werden.

• Propofol und Benzodiazepine haben ein vergleichbares Sicherheitsprofil bei signifikant verkürzter Aufwachzeit für Propofol.

• Ketamin-Razemat kann bei kontrollierter Beatmung und additiver Sedierung mit GABA-Rezeptor-Agonisten auch bei Neurointensivpatienten erwogen werden.

• Der Einsatz von α2-Adrenozeptoragonisten und volatilen Anästhetika entbehrt ausreichender Evidenz.

• Barbiturate sind nur zur Therapie einer therapierefraktären intrakraniellen Hypertension, bei hämodynamischer Stabilität und unter EEG-Monitoring indiziert (keine Prophylaxe!).

• Tägliche Aufwachversuche sollen nur zur neurologischen Beurteilung bei Neurointensivpatienten mit normwertigem ICP und Sympathotonus-Blockade unternommen werden.

Schlüsselwörter

Analgesie - Sedierung - Neurointensivmedizin - intrakranielle Hypertension

Key Words

Analgesia - sedation - neuro intensive care medicine - intracranial hypertension

• Literatur

• 1 Jacobi J, Fraser GL, Coursin DB et al. Clinical practice guidelines for the sustained use of sedatives and analgesics in the critically ill adult. Critical care medicine 2002; 119-141
• 2 Martin J, Heymann A, Bäsell K et al. Evidence and consensus-based German guidelines for the management of analgesia, sedation and delirium in intensive care - short version. Ger Med Sci 2010; 8
• 3 Citerio G, Cormio M. Sedation in neurointensive care: advances in understanding and practice. CurrOpinCrit Care 2003; 9: 120-126
• 4 Albanèse J, Viviand X, Potie F et al. Sufentanil, fentanyl, and alfentanil in head trauma patients: a study on cerebral hemodynamics. Crit Care Med 1999; 27: 407-411
• 5 Roberts DJ, Hall RI, Kramer AH et al. Sedation for critically ill adults with severe traumatic brain injury: a systematic review of randomized controlled trials. Crit Care Med 2011; 39: 2743-2751
• 6 Egerod I, Jensen MB, Herling SF, Welling K-L. Effect of an analgo-sedation protocol for neurointensive patients: a two-phase interventional non-randomized pilot study. Crit Care 2010; 14
• 7 Karabinis A, Mandragos K, Stergiopoulos S et al. Safety and efficacy of analgesia-based sedation with remifentanil versus standard hypnotic-based regimens in intensive care unit patients with brain injuries: a randomised, controlled trial [ISRCTN50308308]. Crit Care 2004; 8: 268-280
• 8 Kelly DF, Goodale DB, Williams J et al. Propofol in the treatment of moderate and severe head injury: a randomized, prospective double-blinded pilot trial. JNeurosurg 1999; 90: 1042-1052
• 9 Marik PE. Propofol: therapeutic indications and side-effects. Curr Pharm Des 2004; 10: 3639-3649
• 10 Mirski MA, Hemstreet MK. Critical care sedation for neuroscience patients. J NeurolSci 2007; 261: 16-34
• 11 Cremer OL, Moons KG, Bouman EA, Kruijswijk JE et al. Long-term propofol infusion and cardiac failure in adult head-injured patients. Lancet 2001; 357: 117-118
• 12 Schwere unerwünschte Arzneimittelwirkungen nach Propofol-Infusionen zur SedierungDtschÄrztebl. 2004 50. 1-2
• 13 Forster A, Juge O, Morel D. Effects of midazolam on cerebral hemodynamics and cerebral vasomotor responsiveness to carbon dioxide. J Cereb Blood Flow Metab 1983; 3: 246-249
• 14 Sanchez-Izquierdo-Riera JA, Caballero-Cubedo RE, Perez-Vela JL et al. Propofol versus midazolam: safety and efficacy for sedating the severe trauma patient. AnesthAnalg 1998; 86: 1219-1224
• 15 Gu J-W, Yang T, Kuang Y-Q et al. Comparison of the safety and efficacy of propofol with midazolam for sedation of patients with severe traumatic brain injury: a meta-analysis. J Crit Care 2014; 29: 287-290
• 16 Takeshita H, Okuda Y, Sari A. The effects of ketamine on cerebral circulation and metabolism in man. Anesthesiology 1972; 36: 69-75
• 17 Sari A, Okuda Y, Takeshita H. The effect of ketamine on cerebrospinal fluid pressure. AnesthAnalg 1972; 51: 560-565
• 18 Belopavlovic M, Buchthal A. Modification of ketamine-induced intracranial hypertension in neurosurgical patients by pretreatment with midazolam. ActaAnaesthesiolScand 1982; 26: 458-462
• 19 Adams HA, Werner C. [From the racemate to the eutomer: (S)-ketamine. Renaissance of a substance?]. Anaesthesist 1997; 46: 1026-1042
• 20 Långsjö JW, Kaisti KK, Aalto S et al. Effects of subanesthetic doses of ketamine on regional cerebral blood flow, oxygen consumption, and blood volume in humans. Anesthesiology 2003; 99: 614-623
• 21 Wang X, Ding X, Tong Y et al. Ketamine does not increase intracranial pressure compared with opioids: meta-analysis of randomized controlled trials. J Anesth 2014; 28: 821-827
• 22 Himmelseher S, Durieux ME. Revising a dogma: ketamine for patients with neurological injury?. AnesthAnalg 2005; 101: 524-534
• 23 Schmittner MD, Vajkoczy SL, Horn P et al. Effects of fentanyl and S(+)-ketamine on cerebral hemodynamics, gastrointestinal motility, and need of vasopressors in patients with intracranial pathologies: a pilot study. J NeurosurgAnesthesiol 2007; 19: 257-262
• 24 Pandharipande PP, Pun BT, Herr DL et al. Effect of sedation with dexmedetomidine vs lorazepam on acute brain dysfunction in mechanically ventilated patients: the MENDS randomized controlled trial. JAMA 2007; 298: 2644-2653
• 25 Riker RR, Shehabi Y, Bokesch PM et al. Dexmedetomidine vs midazolam for sedation of critically ill patients: a randomized trial. JAMA 2009; 301: 489-499
• 26 Venn RM, Bradshaw CJ, Spencer R et al. Preliminary UK experience of dexmedetomidine, a novel agent for postoperative sedation in the intensive care unit. Anaesthesia 1999; 54: 1136-1142
• 27 Wang X, Ji J, Fen L, Wang A. Effects of dexmedetomidine on cerebral blood flow in critically ill patients with or without traumatic brain injury: a prospective controlled trial. Brain Inj 2013; 27: 1617-1622
• 28 James ML, Olson DM, Graffagnino C. A pilot study of cerebral and haemodynamic physiological changes during sedation with dexmedetomidine or propofol in patients with acute brain injury. Anaesth Intensive Care 2012; 40: 949-957
• 29 Turner BK, Wakim JH, Secrest J, Zachary R. Neuroprotective effects of thiopental, propofol, and etomidate. AANA J 2005; 73: 297-302
• 30 Roberts I. Barbiturates for acute traumatic brain injury. Cochrane Database SystRev CD 000033 2000;
• 31 Brain Trauma Foundation, American Association of Neurological Surgeons, Congress of Neurological Surgeons, Joint Section on Neurotrauma and Critical Care, AANS/CNS. Bratton SL, Chestnut RM et al. Guidelines for the management of severe traumatic brain injury. XI. Anesthetics, analgesics, and sedatives. Journal of neurotrauma 2007; 71-76
• 32 Hocker S, Wijdicks EFM, Rabinstein AA. Refractory status epilepticus: new insights in presentation, treatment, and outcome. Neurol Res 2013; 35: 163-168
• 33 Bösel J, Purrucker JC, Nowak F et al. Volatile isoflurane sedation in cerebrovascular intensive care patients using AnaConDa(®): effects on cerebral oxygenation, circulation, and pressure. Intensive Care Med 2012; 38: 1955-1964
• 34 Purrucker JC, Renzland J, Uhlmann L et al. Volatile sedation with sevoflurane in intensive care patients with acute stroke or subarachnoid haemorrhage using AnaConDa®: an observational study. Absalom AR, editor. Br J Anaesth 2015; 114: 934-943
• 35 Villa F, Iacca C, Molinari AF et al. Inhalation versus endovenous sedation in subarachnoid hemorrhage patients: effects on regional cerebral blood flow. Crit Care Med 2012; 40: 2797-2804
• 36 Payen JF, Bru O, Bosson JL et al. Assessing pain in critically ill sedated patients by using a behavioral pain scale. Crit Care Med 2001; 29: 2258-2263
• 37 Yu A, Teitelbaum J, Scott J, Gesin G et al. Evaluating pain, sedation, and delirium in the neurologically critically ill-feasibility and reliability of standardized tools: a multi-institutional study. Crit Care Med 2013; 41: 2002-2007
• 38 Gélinas C, Fillion L, Puntillo KA, Viens C, Fortier M. Validation of the critical-care pain observation tool in adult patients. Am J Crit Care 2006; 15: 420-427
• 39 Riker RR, Fugate JE. Participants in the International Multi-disciplinary Consensus Conference on Multimodality Monitoring. Clinical monitoring scales in acute brain injury: assessment of coma, pain, agitation, and delirium. Neurocrit Care 2014; 21 (Suppl. 02) 27-37
• 40 Chatelle C, Majerus S, Whyte J, Laureys S, Schnakers C. A sensitive scale to assess nociceptive pain in patients with disorders of consciousness. J NeurolNeurosurgPsychiatr 2012; 83: 1233-1237
• 41 Chatelle C, De Val MD, Catano A et al. Is the Nociception Coma Scale-Revised a Useful Clinical Tool for Managing Pain in Patients with Disorders of Consciousness?. Clin J Pain May 28. [Epub ahead of print] 2015;
• 42 Schnakers C, Chatelle C, Majerus S et al. Assessment and detection of pain in noncommunicative severely brain-injured patients. Expert Rev Neurother 2010; 10: 1725-1731
• 43 Ely EW, Truman B, Shintani A et al. Monitoring sedation status over time in ICU patients: reliability and validity of the Richmond Agitation-Sedation Scale (RASS). JAMA 2003; 289: 2983-2991
• 44 Riker RR, Picard JT, Fraser GL. Prospective evaluation of the Sedation-Agitation Scale for adult critically ill patients. Crit Care Med 1999; 27: 1325-1329
• 45 Deogaonkar A, Gupta R, DeGeorgia M et al. Bispectral Index monitoring correlates with sedation scales in brain-injured patients. CritCare Med 2004; 32: 2403-2406
• 46 Olson DM, Thoyre SM, Peterson ED, Graffagnino C. A randomized evaluation of bispectral index-augmented sedation assessment in neurological patients. Neurocrit Care 2009; 11: 20-27
• 47 Sharshar T, Citerio G, Andrews PJD et al. Neurological examination of critically ill patients: a pragmatic approach. Report of an ESICM expert panel. Intensive Care Med 2014; 40: 484-495
• 48 Stocchetti N, Pagan F, Calappi E et al. Inaccurate early assessment of neurological severity in head injury. J Neurotrauma 2004; 21: 1131-1140
• 49 Arias-Rivera S, Sánchez-Sánchez MDM, Santos-Díaz R et al. Effect of a nursing-implemented sedation protocol on weaning outcome. Crit Care Med 2008; 36: 2054-2060
• 50 Marshall J, Finn CA, Theodore AC. Impact of a clinical pharmacist-enforced intensive care unit sedation protocol on duration of mechanical ventilation and hospital stay. Crit Care Med 2008; 36: 427-433
• 51 Quenot J-P, Ladoire S, Devoucoux F et al. Effect of a nurse-implemented sedation protocol on the incidence of ventilator-associated pneumonia. Crit Care Med 2007; 35: 2031-2036
• 52 Hsiang JK, Chesnut RM, Crisp CB et al. Early, routine paralysis for intracranial pressure control in severe head injury: is it necessary?. Crit Care Med 1994; 22: 1471-1476
• 53 Kress JP, Pohlman AS, O'Connor MF, Hall JB. Daily interruption of sedative infusions in critically ill patients undergoing mechanical ventilation. N Engl J Med 2000; 342: 1471-1477
• 54 Girard TD, Kress JP, Fuchs BD et al. Efficacy and safety of a paired sedation and ventilator weaning protocol for mechanically ventilated patients in intensive care (Awakening and Breathing Controlled trial): a randomised controlled trial. Lancet 2008; 371: 126-134
• 55 Mehta S, Burry L, Cook D et al. Daily sedation interruption in mechanically ventilated critically ill patients cared for with a sedation protocol: a randomized controlled trial. JAMA 2012; 308: 1985-1992
• 56 Burry L, Rose L, McCullagh IJ et al. Daily sedation interruption versus no daily sedation interruption for critically ill adult patients requiring invasive mechanical ventilation. Burry L, editor. Cochrane Database Syst Rev CD 009176 2014; 7
• 57 Stover JF. Arousal from sedation in wake-up tests requires careful risk stratification. Crit Care Med 2012; 40: 338-340
• 58 Skoglund K, Enblad P, Marklund N. Effects of the neurological wake-up test on intracranial pressure and cerebral perfusion pressure in brain-injured patients. Neurocrit Care 2009; 11: 135-142
• 59 Skoglund K, Enblad P, Hillered L, Marklund N. The neurological wake-up test increases stress hormone levels in patients with severe traumatic brain injury. Crit Care Med 2012; 40: 216-222