Interprofessional Trauma Conference September 28th 2018 Montreal

Transcription

1 Interprofessional Trauma Conference September 28th 2018 Montreal Marc Perreault & Marc Alexandre Duceppe ICU Pharmacists MGH & RVH-CUSM Faculté de Pharmacie Université de Montréal

2 I have no potential conflict of interest to declare Name of the corporations Type of affiliation (funds, fees, speader, holding shares in actions, others ) Date Hospira/Pfizer Canada Investigator-initiated Grant

3 I have no potential conflict of interest to declare 3

4 Upon attending this session, the participant should be able to: 1- Recognize which patients are at risk of IWS through identification of risk factors 2- Recognize the constellation of signs and symptoms associated with IWS 3- Understand the modalities required to minimize such syndrome

5 Define Iatrogenic Withdrawal Syndrome (IWS) Present its epidemiology and risk factors Describe its symptomatology Differentiate the pediatric and adult symptomatology Propose therapeutic modalities to prevent or treat IWS

6 Reade MC & Finfer S. NEJM 2014; 370: Anand KJS et al. Pediatrics 2010;125(5):e

7 2013 SCCM Guidelines: Era of analgesia-first and light sedation Recommend that opioids and sedatives administered for prolonged periods be tapered over several days Recognize the lack of data in critically ill adults 2017: Next steps in ICU Pain Research Characterization of opioid withdrawal in patients receiving at least 72 hours of opioids Need a descriptive study first 2018: SCCM Guidelines CCM 2013;41: ICM 2017;43: CCM 2018; 46: e

8 Pediatrics: Mixed withdrawal (opioids and benzodiazepines): Incidence ranging from % of patients Using validated tools: Studies using WAT-1 (N=5): 37-77% Studies using SOS (N=4): % Opioids alone Incidence of 44% in 1 study Duceppe et al Manuscript submitted for publication Fisher et al. Heart Lung 2013; 42:

9 Adults: Retrospective studies (N=4): Mixed withdrawal in % of patients Prospective studies (N=2): Mixed withdrawal in % of patients Both studies included trauma patients (40-100% of included patients) Duceppe et al Manuscript submitted for publication Wang et al. Ann Intensive Care 2017; 7:88 Arroyo-Novoa et al. Crit Care Med 2018; 46(Suppl 1):791

10 IWS: Related to age (immaturity of receptors, messengers, transcription factors) Less frequent problem in adults due to shorter duration of opioids/sedatives use Identification of cases is challenging Opioids mixed with sedatives and other Rx Alcohol / illicit drugs withdrawal Lack of clinical tools to screen patients Symptoms of IWS overlap with other problems (agitation, delirium, distress, pain) Unclear impact of this syndrome on clinical outcomes

11 Abrupt cessation or reversal with antagonist (naloxone / flumazenil) Rapid dose de-escalation Most studies looked at a reduction of 10 %/ hourly rate Transition from IV to PO/PT Altered GI absorption (rapid transit time) Delayed IWS due to: Organ dysfunction; Reduced clearance; Active metabolites Underlying condition: need to be on opioids/benzodiazepines for long enough Galinkin & Koh Pediatrics 2014; 133:

12 CNS stimulation Agitation Anxiety Irritability Inconsolable crying Grimacing Restlesness Pupillary dilatation Sleep disturbances Tremors Mouvement disorders Hallucinations Delirium Seizures Sympathetic activation Hypertension Tachycardia Tachypnea Sweating Fever GI disturbance Vomiting Diarrhea Gagging/retching Poor feeding tolerance Devlin et al. CCM 2010; 38(Suppl): S Galinkin & Koh. Pediatrics 2014: 133(1):

13 Systematic reviews Frequent risk factors: age, duration of therapy, cumulative dose Multivariate analysis: Age: 2wks-6mths vs 6mths-1.99y vs 2y-5.99 y vs 6y y Cognitive impairment # days of sedation exposure Mean daily opioid dose pre weaning # days on ECMO (duration of exposure) Best et al CCM 2017; 45(1): e7-e15 Best et al. Ped CCM 2015; 16: Duceppe et al Manuscript submitted for publication

14 Limited data No distinction between opioids and benzo weaning Cumulative opioid dose prior to weaning (mcg/kg) Duration of opioid infusion until 1st wean (h) IWS negative =45 IWS positive n=9 p-value Duration of MV (h) Multivariate analysis: Dose of opioids (OR 2.72; 95 % CI ) Wang et al. Ann Intens Care 2017; 7:88 Rouzé et al.université Lille

15 Two validated tools available: SOS: Sophia Observation Withdrawal Symptoms scale WAT-1: Withdrawal Assessment Tool Most used: WAT-1 Based on a list of signs and symptoms None of these tools have been validated against a blinded clinician Neither differentiates between opioids and benzo withdrawal

16 WAT-1 Tool 11 item tool - total score = 12 Performed BID Trigger: From 1st day of weaning If received opioids ± benzos by infusion or regular dosing for > 5 days Continue up to 72 hours post last dose If Score 3: IWS +

17 Capilnean et al Manuscript submitted for publication Currently - no tools available Validation of WAT-1 tool in adults ICU pts Gold standard: DSM-5 criteria for Opioid withdrawal 181 Blinded and independently performed evaluations in 52 patients Performance of the WAT-1 vs Gold Standard Sensitivity: 50 % Specificity: 65.9 %

18 Not all items in the WAT-1 scale are clinically relevant in the adults Brings to question the need for assessing the S & S of withdrawal in adults

19 Adults patients from RVH and MGH 72 hours of MV + regular opioids±sedatives Trigger to start IWS assessment: Weaning by 10 % of opioid dose IWS assessment: Daily DSM-5 Concurrently: Daily collection of Signs and symptoms by blinded pharmacy resident + bedside RN

20 Rouzé et al.: N= 274 pts sedated with remifentanil ± midazolam 54 developed IWS (19.7%) vs 220 did not develop IWS Outcomes: No differences in reintubation & tracheostomy rates No difference in length of MV or ICU stay Wanzuita et al.: N= 75 pts sedated with fentanyl > 5 days IWS not assessed Randomized to oral methadone or placebo Outcomes: MV Weaning time shorter in those receiving methadone Rouzé et al Université Lille Wanzuita et al. Crit Care 2012;16: R49

21 Weaning protocol according to exposure to opioids/benzos Reduction of dose by % depending on exposure Rescue opioid or benzo may be required with ongoing IWS assessment Approach: Go low, Go Slow Conversion to long acting opioids (methadone) or benzos (clorazepate/diazepam) Uncertainties: Conversion ratio of fentanyl to oral methadone Methadone weaning

22 α-agrenergic central agonist: Clonidine, dexmedetomidine May facilitate weaning and prevent IWS versus masking the catecholamine surge associated with weaning Role in IWS: part of a multimodal approach to IWS Associated with hemodynamic effects

23 Incidence of IWS: Appears to be rare overall in the critically ill adult Suspicion in those exposed with MV and opioids for 72 hours (i.e. trauma pts) Risk factors: related to dose and duration Impact of IWS on clinical outcomes: LOS? Need of a clinical bedside tool / biomarker Treatment modalities include: Weaning strategies with prn rescue Use of clonidine Role of methadone?

24 Tolerance: Decreased clinical effects after prolonged exposure Withdrawal: Clinical syndrome after stopping, reducing or reversing a medication after prolonged exposure Dependence: Physiologic and biochemical adaptation of neurons causing withdrawal or abstinence syndrome upon cessation Tachyphylaxis: Loss of drug effects caused by compensatory neurophysiologic mechanisms Addiction: Chronic syndrome of dependence and craving a driug for its euphoric or sedative properties