5Local anestheticsDose-dependent blockage of sodium channels in neuronsAmides and esters (amides less allergenic)Amides:Lidocaine, bupivacaine, prilocaineEsters: NovocaineLidocaine dosing: 5 mg/kg without epi7 mg with epi
6NSAIDS Conventional Cox inhibitors Cox 2 inhibitors Decreased incidence of GI bleedingDidn’t inhibit platelet aggregationInitial data on side effects was on usage for greater than 1-2 yearsNow some data on side effects as analgesics for CABG patients
7Gabapentin/Pregabalin How do they work?Who knows?Presynaptic binding to calcium channels in brainDecrease excitatory transmission
8Narcotics Morphine Fentanyl Hydromorphone All work on mu receptors Decrease responsiveness of resp center to CO2Stimulate medullary chemoreceptor trigger zoneIncrease sphincter tone and decrease peristalsis
9Opiate Analgesic Options: Fentanyl, Morphine, Hydromorphone Rapid onsetXRapid offsetX*Avoid in renal diseaseX**Preload reductionAvoid in hemodynamic instabilityEquivalent doses100 mcg1.5 mg10 mg* Offset prolonged after long-term use** Active metabolite accumulation causes excessive narcosis
10Rescue/Bolus DosesMSO mg-0.3 mg/kg IV (70 kg – 7-21 mg IV!!!) – I give 5Fentanyl mg IVDilaudid mg/kg IV (70 kg – mg IV)
11PCAMSO4Dose 1.5 mgLockout 7 min4 hr limit 30How do you adjust?
12PCA Fentanyl Dose 20 mcg Lockout 7 min 4 hour dose 300 mcg When do you use it?
21Case 320 y.o. man MCC intubated in field for combativeness, open femur, SAH and L cerebral contusion, etoh 498What’s going to happen to him tonight?
22Case 3 Back from the OR Ex-fix, EVD with ICP 16 What meds will you write for? What do you have to treat?
23Sedation Options: Propofol Pharmacology: GABA agonistPharmacokinetics/dynamics: onset minutes, terminal half-life 6 hours, duration 10 minutes, hepatic metabolismBenefitsRapid onset and offset and easily titratedHypnotic and antiemeticCan be used for intractable seizures and elevated intracranial pressureRisksNot reliably amnestic, especially at low dosesNO analgesia!HypotensionHypertriglyceridemia; lipid source (1.1 kcal/ml)Respiratory depressionPropofol Infusion Syndrome- Cardiac failure, rhabdomyolysis, severe metabolic acidosis, and renal failure- Caution should be exercised at doses > 80 mcg/kg/min for more than 48 hours- Particularly problematic when used simultaneously in patient receiving catecholamines and/or steroids
24Sedation Options: Benzodiazepines (Midazolam and Lorazepam) Pharmacokinetics/dynamicsLorazepam: onset minutes, half-life 10 hours, glucuronidatedMidazolam: onset minutes, half-life 3 hours, metabolized by cytochrome P450, active metabolite (1-OH) accumulates in renal diseaseBenefitsAnxiolyticAmnesticSedatingRisksDeliriumNO analgesiaExcessive sedation: especially after long-term sustained usePropylene glycol toxicity (parenteral lorazepam): significance uncertain- Evaluate when a patient has unexplained acidosis- Particularly problematic in alcoholics (due to doses used) and renal failureRespiratory failure (especially with concurrent opiate use)Withdrawal
25Case 3 Continuous infusion Fentanyl 1 mcg/kg/hr MS04 1-5 mg/hr Midazolam 1-4 mg/hrLorazepam 1-4 mg/hrPropofol – mcg/kg/min (packaged at 10mg/cc; approx cc/hr for 70 kg pt)
26Overview of SCCM Algorithm 1234Jacobi J, Fraser GL, Coursin D, et al. Crit Care Med. 2002;30:
30Atypical Antipsychotics: Quetiapine, Olanzapine, Risperidone, Ziprasidone Mechanism of action unknownLess movement disorders than haloperidolEnhanced effects on both positive (agitation) and negative (quiet) symptomsEfficacy = haloperidol?One prospective randomized study showing equal efficacy of olanzapine to haldol with less EPSIssuesLack of available IV formulationTroublesome reports of CVAs, hyperglycemia, NMSTitratability hampered- QTc prolongation with ziprasidone IM- Hypotension with olanzapine IM
31HaloperidolNo prospective randomized controlled trials in ICU delirium> 700 published reports involving > 2,000 patientsThe good:Hemodynamic neutralityNo effect on respiratory driveThe bad:QTc prolongation and torsades de pointesNeuoroleptic malignant syndrome - only three cases with IV haloperidolExtrapyramidal side effects - less common with IV than oral haloperidol
33Opiate and Benzodiazepine Withdrawal Frequency related to dose and duration32% if receiving high doses for longer than a weekOnset depends on the half-lives of the parent drug and its active metabolitesClinical signs and symptoms are common among agentsCNS activation: seizures, hallucinations,GI disturbances: nausea, vomiting, diarrheaSympathetic hyperactivity: tachycardia, hypertension, tachypnea, sweating, feverNo prospectively evaluated weaning protocols available% daily decrease in dose% initial decrease in dose with additional daily reductions of %Consider conversion to longer acting agent or transdermal delivery form
34Protocols and Assessment Tools SCCM practice guidelines can be used as a template for institution-specific protocols.Titration of sedatives and analgesics guided by assessment tools:Validated sedation assessment tools (Ramsay Sedation Scale [RSS], Sedation-Agitation Scale [SAS], Richmond Sedation-agitation Scale [RSAS], etc.)- No evidence that one is preferred over anotherPain assessment tools - none validated in ICU (numeric rating scale [NRS], visual analogue scale [VAS], etc.)
35Daily Goal is Arousable, Comfortable Sedation Sedation needs to be protocolized and titrated to goal:Lighten sedation to appropriate wakefulness daily.Effect of this strategy on outcomes:One- to seven-day reduction in length of sedation and mechanical ventilation needs50% reduction in tracheostomiesThree-fold reduction in the need for diagnostic evaluation of CNS
36Appropriate Recall May be Important Factual memories (even unpleasant ones) help to put ICU experience into perspectiveDelusional memories risk panic attacks and PTSDThe optimal level of sedation for most patients is that which offers comfort while allowing for interaction with the environment.
37Recall in the ICUSome degree of recall occurs in up to 70% of ICU patients.Anxiety, fear, pain, panic, agony, or nightmares reported in 90% of those who did have recall.Potentially cruel:Up to 36% recalled some aspect of paralysis.Associated with PTSD in ARDS?41% risk of recall of two or more traumatic experiences.Associated with PTSD in cardiac surgery
38What We Know About ICU Agitation/Discomfort Prevalence50% incidence in those with length of stay > 24 hoursPrimary causes: unrelieved pain, delirium, anxiety, sleep deprivation, etc.Immediate sequelae:Patient-ventilator dyssynchronyIncreased oxygen consumptionSelf (and health care provider) injuryFamily anxietyLong-term sequelae: chronic anxiety disorders and post-traumatic stress disorder (PTSD)
39Opiates Benefits Risks Relieve pain or the sensibility to noxious stimuliSedation trending toward a change in sensorium, especially with more lipid soluble forms including morphine and hydromorphone.RisksRespiratory depressionNO amnesiaPruritusIleusUrinary retentionHistamine release causing venodilation predominantly from morphineMorphine metabolites which accumulate in renal failure can be analgesic and anti-analgesic.Meperidine should be avoided due to neurotoxic metabolites which accumulate, especially in renal failure, but also produces more sensorium changes and less analgesia than other opioids.