Transcript Management of Abstinence

Management of
Abstinence
Bradley J. Phillips, MD
Substance Abuse
• Alcohol Abuse
• 76 million people in the US
• MVC leading cause of death
• 50% of MVC involve alcohol
• 2/5 Americans involved
• 67% of home, fire, and job injuries
• Illicit Drug Abuse
• cocaine > 50% of trauma
• cocaine > 80% of violent crime
Pitfalls of Intoxication
• Increased incidence of diagnostic errors
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desire to “treat and street”
assuming just a “repeater”
failure to recognize serious neurologic lesions
decreased pain perception
Acute/Chronic EtOH Effects on
Physiology
• Respiratory
• “snoring” = partial airway obstruction
• prone to aspirate
• Cardiovascular
• decreased compensatory response to
hemorrhage
• increased arrhythmias
• increased cardiomyopathy
Acute/Chronic EtOH Effects on
Physiology
• Neurologic
• Korsakoff’s syndrome
• Wernicke’s syndrome
• peripherial neuropathy
• GI
• cirrhosis
• GI bleeds
• varices
• peptic ulcers
Acute/Chronic EtOH Effects on
Physiology
• Metabolism
• alcohol ketoacidosis
• hypoglycemia
• Hematology
• coagulopathies
• anemia
• poor resistance to infection
Illicit Drugs Effects on Physiology
• Cocaine/amphetamines/hallucinogens
• respiratory difficulty
• tachycardia
• hypertension
• Narcotics/barbiturates/tranquilizers
• hypoventilation
• bradycardia
• hypotension
Cocaine
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Local anesthetic and sympathomimetic
Hyperdynamic cardiovascular response
CVA (hypertensive crisis)
Myocardial infarcts
Aortic dissection
Pulmonary edema/bronchospasm
Rhabdomyolysis
GI ischemia/perforations
Mental status (judgement, paranoia)
Opiates
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Decreased mental status
Hypotension
Hypovolemia
Pulmonary congestion
Infectious (heroin)
Historical Withdrawal
• Victor and Adams, 1953
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Ist comprehensive account
4 “states”
occur separately or in combinations
mortality = 15% (delirium state)
Day 1 Day 2 Day 3 Day 4 Day 5 Day 6 Day 7
tremulous
hallucinatory
epileptic
delirious
“Modern” EtOH Withdrawal
• Acute Withdrawal
• hours to days
• irritability, tremulous, tachycardia
• Delirium tremens (DT’s)
• usually > 48 hrs
tremors
confusion
delusions
tachycardia
hypertension
hyperreflexia
hallucinations
seizures
“Modern” Time Course
Foy, Kay, Taylor. QJM, 1997
Diagnosis
• Symptoms
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drug craving
restlessness
irritability
dec. pain tolerance
nausea
cramps
anxiety
myoclonus
delirium
• Signs
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tachycardia
sweating
vomiting
diarrhea
hypertension
fever
seizure
tachypnea
Evaluation
• History
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timing of last usage
amount
previous withdrawal/seizures
family member informant
• Labs
• EtOH/toxicology screen (blood/urine)
• CBC/coags
• electrolytes/bun/cr/mg/phos/LFT’s
Differential Dx
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Hypoxia
Shock/hypovolemia
Head trauma
Sepsis
Hypoglycemia
Electrolyte abnormalities
• Withdrawal
DT’s Complications
• Significant co-morbidity
• Cardiac collapse
• CI 36%
• O2 consumption 25%
• Seizures
• Renal failure
• Mortality
• 1 to 15%
Onset/Duration of Complications
Duration (hrs.)
Time to Onset (hrs.)
Foy, Kay, Taylor. QJM, 1997
Pharmacological Management
• Shown beneficial
• benzodiazepines
• alpha-adrenergic
agonist
• anti-seizures
• Propofol
• barbiturates
• neuroleptics
• clomethiazole
• No efficacy (humans)
• beta-adrenergic
antagonist
• Ca-channel blockers
• ethyl alcohol
• magnesium
• thiamine
Benzodiazepines
• Moskowitz et al, Alcohol Clin Exp Res,
1983 - 81 studies
• Only proven efficacious drug
• Drugs of choice
• Safer than other drugs if taken in
excess
Benzodiazepines
• Pharmacological characteristics
• CNS and peripherial interaction with GABA
receptors
• no particular one better at preventing
withdrawal symptoms
• ? longer-acting better at preventing seizures
• no data on reducing delirium
• duration of action dependent on lipophilicity,
volume of distribution and half-life
• hepatic metabolism only
Benzodiazepines
• Long-acting
• Chlordiazepoxide
(Librium)
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active metabolites
t1/2 = 1-8 days
po/IV/IM
avoid IM
• Diazepam (Valium)
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active metabolites
t1/2 = 25-100 hrs
po/IV/IM
avoid IM
• Short-acting
• Lorazepam (Ativan)
• no active metabolites
• t1/2 = 10-20 hrs.
• slower onset of
action
• po/IV/IM
• Midazolam (Versed)
• active metabolites
• t1/2 = < 12 hrs
• IV/IM
Benzodiazepines
• Method of Dosing
• scheduled vs. prn
• Sellers et al, Clin Phar Ther, 1983
− valium 20 mg q 1-2 hrs prn
− successful = 72% (valium) vs 56% (placebo)
− 90% improved in 30 hrs.
• Saitz et al, JAMA, 1994
− po Librium scheduled vs prn
− scheduled = 68 hrs. vs prn = 9 hrs.
− scheduled = 425 mg vs. prn = 100 mg
Benzodiazepines
Foy, Kay, Taylor. QJM, 1997
Benzodiazepines
• Adverse effects
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respiratory depression
cardiovascular depression
iatrogenic withdrawal
metabolic acidosis
• propylene glycol
• carrier in diazepam IV
• converted to lactic acid
• also found in silver sulfadiazene, IV nitro,
and etomidate
Barbiturates
• Used by 10% of detoxification programs
• No controlled studies for effectiveness
• Advantages
• low abuse potential
• cheap
• well-documented anti-seizure
• Disadvantages
• greater respiratory depression
• cardiovascular depression
• lower safety profile than benzodiazepines
Clonidine
• Alpha1-adrenergic agonist
• Controlling withdrawal symptoms/signs
• superior to placebo
• equivalent to carbazepine + neuroleptic
• superior to clomethiazole
• Controlling delirium/seizures
• no adequate sized studies
• Clonidine vs benzodiazepine
• only one randomized study
• no significant difference
• seizure patients excluded
Neuroleptics
• No controlled studies
• Early studies less effective than benzos
• Advantages
• effective for psychosis
• safe respiratory/cardiovascular profile
• Disadvantages
• increased seizures (thorazine,promazine)
• extra-pyramidal side-effects
Carbamazepine
• Used in Europe
• Efficacious vs clomethiazole/placebo
• Advantages
• lower abuse potential
• less CNS depression
• Disadvantages
• side-effects = N/V, vertigo, rash
• 50% stop therapy secondary SE
• IV not available in US
Propofol
• Activates GABA-A receptor
• Effectiveness
• no controlled studies
• ? benefit in refractory withdrawal
• adjunct to primary therapy
• Advantage
• short-acting
• easily titratable
• Disadvantage
• tolerance
• cost
Alternative Agents
• Beta-adrenergic antagonists
• IV/po differential effectiveness
• studies support effective for tremors
• Advantages
• ? may be effective for mild withdrawal
• no addiction potential
• Disadvantages
• cardiovascular effects
• cause hallucinations
• no role for mod-severe withdrawal
Alternative Agents
• Clomethiazole (Used in Europe)
• effective as benzos and barbiturates
• severe adverse effects
• Ethyl alcohol
• no trials on safety/efficacy
• numerous adverse effects
• Magnesium
• no reduction in delirium/seizures
• Thiamine
• no reduction in delirium/seizures
• prevention of Wernicke-Korsakoff
Recommendations
• Benzodiazepines
• ativan/valium prn
• Clonidine
• adjunctive agent
• excellent control of hyperadrenergic state
• po preferred over patch
• Neuroleptics
• excellent control of psychosis
• possible side-effects (less likely with Haldol)
• Propofol/barbiturates
• 2nd line adjuncts
Recommendations
• Dosing
• Closely monitored setting
• prn dosing
• IV for acute withdrawal/inability to
tolerate po
• Untrained monitoring setting
• fixed-scheduled po dosing
Outcomes
• Increased mortality
• Luna et al, J Trauma, 1984
• double mortality vs sober with similar injuries
• Waller et al, JAMA, 1986
• 1.7 to 2.1x mortality vs. matched sober MVC
• Tinkoff, Ann Surg, 1990
• 30-40% mortality in cirrhotic trauma
• sepsis and MSOF
• predictors - ascites, PT, bilirubin, laparotomy
Delay in Treatment
Foy, Kay, Taylor. QJM, 1997
Length of Stay
Foy, Kay, Taylor. QJM, 1997
Risk Factors
Foy, Kay, Taylor. QJM, 1997
ICU Withdrawal Syndrome
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Cammarano, Crit Care Med, 1998
Retrospective study
Trauma/surgical ICU
28 mechanically ventilated patients
> 7 day ICU stay
ICU Drug Potencies
Cammarano et al, Crit Care Med, 1998
ICU Withdrawal vs Drug
Non-withdrawal
Withdrawal
Cammarano et al, Crit Care Med, 1998
Duration
Non-withdrawal
Withdrawal
Cammarano et al, Crit Care Med, 1998
Mean Doses
Non-withdrawal
Withdrawal
Cammarano et al, Crit Care Med, 1998
ICU Withdrawal Syndrome
• Results
• 32 % acute withdrawal
• opiates/benzodiazepines
• ICU stay > 7 days
• withdrawal group
• higher daily doses of fentanyl and ativan
• received neuromuscular blockade
• received propofol
• longer duration of agents
ICU Withdrawal Syndrome
• Prevention
• adequate monitoring of level of sedation
• avoid neuromuscular blockade if possible
• realization of predisposition
• ARDS
• younger patients
• wean opiates/benzo in pts at risk
• 5-10% / day
• ? change to longer acting agent po
• use bolus method over continuous
Questions…?