Sedation and Delirium in the Intensive Care Unit

1. Sedation and Delirium in the Intensive Care Unit • Dr. Omer Mirza

2. Objectives • Pain, sedation and analgesia in the ICU. • Causes and Interactions of Pain, Agitation, and Delirium. • Choice of sedative agent in the ICU. • Prevention and treatment of delirium. • Assessment and monitoring of sedation and delirium. • Prevention and treatment of delirium.

3. Introduction • Pain is the most common memory of ICU stay. • Causes include endotracheal intubations, vascular access attempts etc. • Agitation can precipitate accidental removal of lines and tubes. • Sedatives and analgesics are among the most commonly used medications in the ICU.

4. Early intensive care. • Early intensive care evolved from intraoperative anesthetic care. • Older ventilators poorly synchronized with patients necessitating deeper sedation until reduced and patient waking enough to be extubated. • As such, extensive use of sedation was common. • Over last few decades, with microprocessor controlled ventilators able to better synchronize. • Shorter duration medications exist, allow less given doses.

5. Triads. • Triads of anaesthesia. • Interactions between hypnotics, analgesics and muscle relaxants. Simultaneous dosing allows lower doses of each. • Triads of critical care. • Pain, agitation and delirium and approaches to their management are inextricably linked. • Sedatives should only be used once pain and delirium have been addressed.

6. Pain, sedation and analgesia in the ICU. • Pain is a common occurrence in the ICU. • Standard for pain management is self assessment and reporting. • Hypertension and tachycardia correlate poorly. • Behavioral pain scale and critical care pain observational tool • Consequences of inadequate pain treatment. • Short term • Higher energy expenditure. • Immunomodulation. • Longer term • Possible post traumatic stress disorder.

7. Causes and Interactions of Pain, Agitation and Delirium.

8. Indications for deep sedation • Some patients require continuous deep sedation. • Treatment of intracranial hypertension. • Severe respiratory failure. • Refractory status epilepticus. • Prevention of awareness in patients on paralytics. • Vast majority on mechanical ventilation do not need this. • Minimized sedatives and analgesics. • Lucid, calm, pain-free, interactive and cooperative.

9. Evidence for patterns of sedation • Daily interruption of sedative infusions in critically ill patients undergoing mechanical ventilation. 2000 NEJM. • Less sedation overall. • Fewer days on mechanical ventilation. • Fewer days in the ICU. • Too small sample size to assess differences in mortality or discharge destination. • Reduction in mortality and discharge to home were not significant. • Also...

10. Evidence 2 • Efficacy and safety of a paired sedation and ventilator weaning protocol for mechanically ventilated patients in intensive care. Lancet 2008. • Larger multicenter trial, it combined daily interruption of sedation with daily spontaneous breathing trials. • Daily interruption was associated with reduced administration of benzodiazepine sedative, reduced mechanical ventilation, reduced length of ICU stay and significantly increased survival.

11. Contrary evidence. • Daily sedation interruption in mechanically ventilated critically ill patients cared for with a sedation protocol: a randomized controlled trial. JAMA 2012. • When daily interruption was combined with a protocol to minimize sedation, the total sedative dose was increased and there was no clinical benefit.

12. Conflicting Evidence Parsed • Interpretations. • Daily interruption is only beneficial when it results in a reduction of the total dose of sedative administered. • Daily interruption may be dependent on type of population studied, or adherence to protocol, or management of control group. • Depth of sedation was independently associated with duration of mechanical ventilation, in-hospital mortality, rates of death within 180 days. • Minimizing sedation provides clinical benefit, more ventilator free days, ICU-free days.

13. Choice of sedative agent • Requirements of agent used for patient comfort. • Pain relief. • Quick onset and clearance. • Sedation. • Less active metabolites. • Less hemodynamic effects. • Amnesia. • Does not exist. • Traditionally combination of drugs were used. • Narcotics, benzodiazepines, others (propofol, ketamine etc)

14. Choice of sedative agent • No sedative agent is clearly superior to all others. • Many drugs are routinely used in the ICU. • Narcotics. • Benzodiazepines. • Atypical agents. • Choice of agent is determined by tradition and familiarity than by evidence based practice.

15. Choice of sedation agent • New goals. • Minimizing depth and duration of sedation. • Short acting, rapidly titrated, may be preferred over longer acting compounds, compounds with more active metabolites.

16. Choice of sedation agent • Benzodiazepines. • Midazolam, lorazepam, occasionally diazepam. • GABA receptors. • Propofol. Result in shorter duration of ICU stay over benzo. • Dexmedetomidine. Alpha 2 receptor agonist. Analgesia, less respiratory depression, less delirium, shorter duration of mechanical ventilation. No reduction in ICU or hospital LOS. • Remifentanyl. Half-life of 3 to 4 minutes. Independent of infusion duration or organ function. Evaluated in surgical patient population. Reduced duration of mechanical ventilation and ICU stay.

17. Prevention and treatment of delirium • What is delirium. • Sudden severe confusion and rapid changes in brain function that occur with physical or mental illness. • What defines delirium. • Disturbance of consciousness. • Change in cognition. • Development over a short period. • Fluctuation. • Cardinal sign. Inattention. • Non specific. Reversible. Many causes. • Diagnosis of delirium is associated with increased mortality.

18. Prevention and treatment of delirium • No diagnostic test. • Incidence estimated at 16% to 89% • Characteristics of the population. • Diagnostic criteria used. • Increased risk with GABA agonists and anticholinergic drugs. • Above risk suggests possible GABAergic and cholinergic neurotransmitter systems may play a contributory role. • Central cholinergic deficiency may be final common pathway. • Alternate hypothesis • Excess dopaminergic activity may contribute. • Direct neurotoxic effects of inflammatory cytokines. • Associated with increased mortality 10%

19. Delirium and MRI Imaging • Studies using MRI on patients with delirium. • Positive association between duration of delirium and both cerebral atrophy and white matter disruption. • Does delirium give rise to changes in brain structure. • Presence of cerebral atrophy and white matter disruption increases susceptibility to delirium.

20. Types of delirium. • Types. • Hypoactive. Inattention. Disordered thinking. Depressed LOC with no agitation. Least likely to survive. But better long term function if survive. • Agitated. Less than 2%. • Mixed. • Differentiating the risk of death contributions from delirium versus severity of disease is difficult. • No causal relationship between delirium and death. • No strong evidence that treatment of delirium improves outcome.

21. Assessment and monitoring of sedation and delirium. • Depth of sedation monitoring is not optimal. • Different scales can be used. • Riker Sedation-Agitation Scale. • Range 1 to 7. target 3-4. • Richmond Agitation-Sedation Scale. • Range -5 to +4. target -2 to 0. • Neither is demonstrably superior. • These two are commonly reported.

22. SASS and RASS

23. Identifying delirium • Not accurately identified in ¾ of patients. • Active screening increases identification. • Tools to identify delirium in psychiatry patients and general medical patients are difficult to use in the ICU. • Severity of illness fluctuates rapidly. • Receive multiple sedatives and analgesics. • Unable to speak with intubation.

24. Tools to identify delirium • Two scales are used. • These are beneficial for research purposes. • May not be more sensitive than a bedside assessment. • However some studies suggest bedside nursing assessment may highly sensitive versus poorly sensitive. • Without a sedation scale, these diagnostic scales do not distinguish between types of delirium.

25. Delirium diagnosis scales • Confusion Assessment Method for the ICU (CAM-ICU). • Intensive Care Delirium Screening Checklist (ICSC). • These dichotomize delirium as present or absent. • Degrees of severity are ignored. • No quantification of of relative improtance of individual elements.

27. Prevention and Treatment of Delirium • Prevention. • Outside the ICU. Steps to reduce delirium. • Repeated re-orientation. • Noise reduction. • Cognitive stimulation. • Vision and hearing aids. • Adequate hydration. • Early mobilization. • Haloperidal prophylaxis. In hip surgery patients. • In the ICU. Early mobility reduces delirium by half.

28. Do we know what works. • Surgical patient population studies. • Low dose haldol. Low dose risperdal. Single dose of ketamine at induction. All reduce incidence of haldol. • Studies done among patients with elective surgical procedures. Not able to be generalized. • Medical patient populations. • Dexmedetomidine or midazolam, similar times at target sedation levels. Less risk of delirium with dexmedetomidine and lower mechanical ventilation times. • Dexmedetomidine versus lorazepam infusion. Former had more time at sedation target, longer survival without delirium or coma.

29. Well Do We? • Dexmedetomidine versus propofol or midazolam. • No difference between proportion of time at target sedation level. • Rates of delirium, anxiety or agitation, • Dexmedetomidine and midazolam equivalent. • Dexmedetomidine lower than with propofol. • At 48 hrs after sedation. No difference between groups.

30. Treatment. • Very little evidence to guide management of established delirium. • Most trials were pilot studies. • None distinguished between hypoactive or hyperactive delirium. • Quetiapine. • Regular haldol versus olanzapine. • Regular haldol, ziprasidone or placebo. • Dexmedetomidine versus haldol and versus midazolam.

31. Quality Improvement. • PAD guidelines. • ABCDE bundle. • Improving team communication. • Standardizing care processes. • Prioritizing methods to lighten sedation. • Facilitate early mobility.

32. Last Words. • Sedation and delirium can have an improtant effect on ICU patient outcomes. • Data suggests best results may be achieved with sedation protocol, monitoring and prompt treatment of pain and delirium, sedatives to a minimum necessary for patient comfort and safety. • Early mobilization when possible.

33. Questions?

34. Thank you. Special debt of gratitude to my colleagues in the respiratory department. For ensuring safety, working to create protocols to standardize care. And strong proponents of lightening sedation and early extubation.