Objectives. Important Principles

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1 Management of the Intubated Patient Christopher J. Edwards, PharmD, BCPS Clinical Pharmacist - Emergency Medicine March 19 th, 2013 REPS EC SAG 2 Objectives Describe the rationale for post intubation analgesia and sedation Compare and contrast various sedatives commonly used in mechanically ventilated patients Design the optimum regimen of sedation and analgesia for the recently intubated patient Important Principles Events prior to intubation can be painful Intubation is painful Procedures done after intubation are painful Analgesia is the cornerstone of post intubation care 1

2 Pain from Endotracheal Intubation Rotondi AJ, et al. Patient s recollections of stressful experiences while receiving prolonged mechanical ventilation in an intensive care unit. Crit Care Med 2002 Endotracheal tube pain, 0 10 scale (25 th and 75 th percentile) ETT pain at its worst = 8 (6, 10) ETT pain at its least = 5 (3, 7) Negative Effects of Poor Pain Control Patients who recalled pain had higher incidence of chronic pain, PTSD symptoms, and lower health related quality of life Schelling et al. CCM Pain response increases catecholamine release, impairs tissue perfusion Deleterious effects on immune response Post-Intubation Analgesia and Sedation in the Emergency Department Weingart GS et al. Estimates of sedation in patients undergoing intubation in US EDs Am J of EM 1,071,000 patients included, 46.4% received sedatives and/or opiates Jordan, B et al. Inadequate provision of postintubation anxiolysis and analgesia in the ED Am J of EM 117 patients, 33% received no anxiolysis, 53% received no analgesia Of 70 patients who received vecuronium, 4% received adequate anxiolysis or analgesia 2

3 Paralytic Choice and Time to Sedation Early initiation of analgesia and sedation is particularly important when long acting paralytics are used Watt JM, et al. Effect of paralytic type on time to post-intubation sedative use in the ED. EMJ Significantly greater time between intubation and initiation of sedation in patients receiving rocuronium compared to succinylcholine Emergency Pharmacists Can Help! Endpoint Before EPh After EPh p value Rate of post 8 (20%) 20 (49%) p = intubation analgesia Sedative or anxiolytic 30 (73%) 21 (51%) p =0.04 without analgesia Time to analgesia after intubation 98 minutes 45 minutes N/A Robey-Gavin, E and Abukar, L. Impact of clinical pharmacists on initiation of postintubation analgesia in the emergency department. Poster presented at ASHP s Midyear Clinical Meeting SCCM Guidelines for Management of Pain, Agitation, and Delirium in ICU Barr J, et al. Critical Care Medicine Preemptive analgesia Opiate based regimens Light level sedation Non-benzodiazapines first line Benzodiazapines second line 3

4 The ED is not the ICU Procedures often performed immediately after intubation Central line placement Radiological i limagingi Lumbar puncture Orthopedic reduction Etc, etc, etc Higher nurse to patient ratios Much shorter length of stay Pain Assessment in Mechanically Ventilated Patients Pain Scales BPS Behavioral Pain Scale CPOT Critical Care Pain Observation Tool Vital signs should prompt further evaluation Respiratory rate Tachycardia Hypertension Diaphoresis Richmond Agitation Sedation Scale (RASS) Score Term Description + 4 Combative Overtly combative, violent, immediate danger to staff + 3 Very Agitated Pulls or removes tube(s) or catheter(s); aggressive + 2 Agitated Frequent non-purposeful movement, fights ventilator + 1 Restless Anxious but movements not aggressive vigorous 0 Alert and Calm -1 Drowsy Not fully alert, but has sustained awakening (eye-opening/eye contact) to voice (>10 seconds) -2 Light sedation Briefly awakens with eye contact to voice (<10 seconds) -3 Moderate sedation Movement or eye opening to voice (but no eye contact) -4 Deep sedation No response to voice, but movement or eye opening to physical stimulation -5 Unarousable No response to voice or physical stimulation 4

5 Important Concept Bolus when patient acutely agitated Titrating drip without bolus leads to slow resolution of agitation Leads to aggressive titration Leads to over sedation\adverse effects Leads to discontinuation of sedation Leads to acute agitation Rinse and repeat Analgesia Opiates Who should receive Almost anyone who is currently intubated Who should not receive Patients currently on naloxone Certain patients intubated for oversedation/intoxication Precautions Can cause sympatholysis leading to hemodynamic instability 5

6 Fentanyl Onset: seconds with bolus dosing hour for bolus doses Extended with prolonged infusion, hepatic impairment Bolus dosing: mcg/kg Continuous infusion starting rate: mcg/kg/hr Less hypotension compared to morphine Potential for chest wall rigidity Hydromorphone Onset: 5-15 minutes with bolus dosing 2 3 hours for bolus doses Intermittent bolus dosing: mg every 1-2 hours Continuous infusion rate: mg/hr Less hypotension compared to morphine Morphine Onset: 5-10 minutes with bolus dosing 3-4 hours for bolus doses Intermittent bolus dosing: 2-4 mg every 1-2 hours Continuous infusion rate: 2 30 mg/hr Accumulation of active metabolite in renal failure Histamine release induced hypotension 6

7 Opiates Opiate Fentanyl Equi- Analgesic Dose 0.1 mg (100 mcg) Onset Elimination Half-Life Bolus Dose sec hr mcg/kg q hr Initial Infusion Rate mcg/kg/hr mg/hr Hd Hydromorphone mg 5 15 min 2 3h hr mg 05 3 /h q 1 2 hr Morphine 10 mg 5 10 min 3 4 hr 2 4 mg q 1 2 hr 2 30 mg/hr Sedatives Propofol Non-benzodiazepine sedative Sedative, hypnotic, anxiolytic, amnestic, antiemetic, and anticonvulsant properties NO analgesic effects Who should get it Patients requiring frequent neurologic examinations Patients with traumatic brain injury Precautions/contraindications Hemodynamic instability Pediatric patients Propofol related infusion syndrome Egg and soy allergic patients 7

8 Propofol Onset: seconds with bolus dosing 3-12 hours with continuous infusion Duration extended with prolonged infusion, higher rate of infusion, excessive lipid stores, older patients Duration decreased in younger patients Bolus dosing: mg/kg Continuous infusion: 5 70 mcg/kg/min Typical starting rate: 20 mcg/kg/min Benzodiazepines GABA-A activation leading to sedative effects Anxiolytic, amnestic, hypnotic, and anticonvulsant properties NO analgesic effect Who should receive Patients who cannot tolerate propofol Patients who do not require frequent awakening Precautions Patients with hepatic failure (prolonged duration) Chronic alcohol/benzo users may require higher doses Midazolam Onset: 2 5 minutes after bolus 3 11 hours Extended with prolonged infusion, higher rate of infusion, older patients, hepatic failure, renal insufficiency Bolus dosing: mg/kg Initial infusion rate: mg/kg/hr Concerns Accumulation of active metabolite in renal insufficiency Tachyphylaxis 8

9 Lorazepam Onset: 3 10 minutes after bolus 8-15 hours Duration extended with prolonged infusion, higher rate of infusion, older patients, hepatic failure, renal insufficiency Bolus dosing: mg/kg q 6 hrs prn Infusion rate: mg/kg/hr Preferred benzodiazepine in hepatic failure Concern for propylene glycol toxicity Dexmedetomidine Selective α2-receptor agonist Sedative, analgesic, sympatholytic properties Lacks amnestic and anticonvulsant properties Who should receive Patients requiring short term, low level sedation Patients who are difficult to wean off of mechanical ventilation Precautions Hemodynamic instability (bradycardia, hypotension) No amnestic effects Dexmedetomidine Onset: 15 minutes after initiation of infusion hours Extended in hepatic insufficiency Bolus not recommended due to adverse hemodynamic effects Continuous infusion: mcg/kg/hr 9

10 Sedatives Agent Onset After Bolus Elimination Half-Life Bolus Dose Maintenance Propofol 0.5-1min 3-12 hr (Short term use) mg/kg 5 70 mcg/kg/ min Dexmedetomidine N/A hr 3.1 Not recommended mcg/kg/hr Midazolam 2 5 min 3 11 hr mg/kg mg/kg/hr Lorazepam 3 10 min 8 15 hr mg/kg (2 mg max) mg/kg/hr (max 10 mg/hr) Ketamine NMDA receptor antagonist Dissociative anesthetic with analgesic, sympathomimetic, and brochodilatory effects Who should receive Patients in status asthmaticus Opioid tolerant patients with uncontrolled pain Precautions May lead to ICU delirium Intracranial and intraocular pressure Ketamine Onset: seconds after bolus dose 2 3 hours Extended in hepatic insufficiency Bolus dosing: mg/kg Continuous infusion: mg/kg/hr 10

11 Non-Pharmacologic Measures Talk to the patient! Optimize ventilator settings Minimize disruptions (if possible) Soft restraints Other Concepts in Post Intubation Management Prevention of ventilator associated pneumonia Oral care early and often Elevate head of the bed at least 30 degrees OG/NG tube placement, gastric suctioning Ocular care Stress ulcer prophylaxis Mechanical ventilation > 48 hours Coagulopathy Conclusions Analgesia and sedation are key to ensuring patient and provider comfort after intubation Keep patient s clinical picture and trajectory in mind when designing regimen Post intubation management is an easy way for emergency pharmacists to make a big impact! 11

12 Further Reading Barr J, Fraser GL, Puntillo K, Ely EW, Gelinas C, Dasta JF, et al. Clinical practice guidelines for the management of pain, agitation, and dlii delirium in adult dl patients in the intensive i care unit. Critical Care Med. 2013; 41: