Conference Lectures

              Rave Drugs-Pharmacological and Anaesthetic Consideration

   Dr Rudrashish Haldar
Assistant Professor
Dept. of Anaesthesiology
SGPGIMS, Lucknow

Rave drugs (also known as “club” or “designer” drugs are a class of illicit drugs which has seen a tremendous spurt in popularity and use amongst youth since 1990’s in the western world. These drugs are made available or distributed in “Rave parties” which are characterized by loud, electronic “techno rock” music (produced by computers with little or no vocals) and held at obscure locations. These drugs seemingly enhance energy, friendliness, stamina and sexual arousal which help the adolescent and young adult participants of such parties to sustain the exhausting lengthy all night dancing sessions. Their use is independent of the variables of age, gender, sexual orientation and race/ethnicity.1 However  both the short term and long term physiological and psychological adverse effects of these drugs are relatively lesser known. Blood borne infections like HIV and hepatitis is higher in subjects abusing these drugs through intravenous route. Moreover monitoring and toxicological screening for these drugs still remains an under researched area and thus this hazard continues to rise unchecked.

Indian Perspective:-
Following the alteration in the social scenario in the last two decades, these drugs made their in-roads in the Indian club scene too. Authentic data in Indian context is lacking and is based on newspaper and police reports. Initial reports implicated regions like Goa and Ahmedabad as the hubs.2 Other regions like Kullu Valley (Himachal Pradesh) 3,Bangalore4 and Pune5 have emerged as rave hotspots. These drugs are considered as status symbol amongst the neo rich youth with an ill conceived notion of being safer from conventional hard drugs like heroine, cocaine etc. Unlike cannabis and opium, these drugs are usually imported or smuggled from neighbouring countries.
Common rave drugs and their pharmacologies:-

  1. Ecstacy (3,4-methylenedioxymethamphetamine, MDMA) : The oldest in this class of drugs, it was first synthesized in 1912 and has been used recreationally since 1970’s for its stimulant and hallucinogenic properties. Street names of these drugs include X,M, E XTC, Rolls, Clarity, Adam, Lover’s speed, hug drug. It is available in tablet/capsule form which can be ingested orally or crushed and snorted or dissolved and injected.6 Structurally related to psychostimulant metaamphetamine and hallucinogen mescaline. It crosses the blood brain barrier and stimulates both CNS and sympathetic system by releasing serotonin, dopamine and norepinephrine and blocking their reuptake inactivation by inhibiting monoamine oxidase.7 Subjective feelings include feeling of empathy, energy, psychomotor drive, positive mood, increased perception and sensory awareness. Toxicity of MDMA is manifested in form of nausea, tachycardia, hypertension, anxiety, bruxism and fatal effects like disseminated intravascular coagulation (DIC), seizures or death. Characteristic effects also include the alteration of body’s temperature regulation capacity leading to hyperthermia which effects the renal, hepatic and cardiovascular changes. This leads to excessive water drinking which causes hyponatremia to which young women are particularly susceptible.8 Since it interferes with its own metabolism, it can lead to buildup of toxic levels on repeated use in a short time. As it acts on the serotoninergic neurons it causes changes in cognitive defects, memory changes and depression. Neurotoxicity has been demonstrated in primates and the same effect may be seen in humans.9 Routine screening for MDMA is difficult as immunoassays fail to detect it in a significant number of  standardized specimen,10  though toxicologists have now developed procedures for detection and quantification.11
  2. Ephedrine: Chemically it is an amphetamine analogue. Often sold in rave parties as herbal ectasy. It mediates its effects through overstimulation of CNS and sympathetic overactivity. Adverse effects include tremulousness, anxiety, agitation and palpitation. Serious events like stroke, seizures, myocardial infarction, hepatitis and sudden death are reported. Toxicologial screening can give a positive test for amphetamines.
  3. GHB (Gamma- hydroxybutyrate): First synthesized in 1960 as an anaesthetic and subsequently became popular as a recreational drug and nutritional supplement for bodybuilders. 12 Street names include G, Liquid ecstacy, Georgia Home Boy, Grievous Bodily Harm, Goop, Gib, Soap and Nitro. It is available as a liquid, white powder (for dissolving in liquids), tablets or capsules. It acts as a CNS suppressant and is structurally related to GABA. 13 Receptor sites highly specific for GHB are present in the hippocampus, cortex and dopaminergic areas. GHB inhibits dopamine release and activates tyrosine hydroxylase thereby increasing central dopaminergic stores. It is often mixed with alcohol to amplify its effects.14. Effects include rapid loss of consciousness or onset of stupor (G-Napping) and antegrade amnesia. 15 Because of the level of incapacitation it produces, memory defects and its rapid clearance from the body it has attained notoriety as “date rape drug”16Toxic effects include sleep, agitations, seizures, GI symptoms, apnoea, bradycardia and coma. It can produce dependence and withdrawl symptoms. Withdrawl symptoms are treated by benzodiazepines and trazodone (for mild symptoms) and barbiturates, high dose benzodiazepines, mood stabilizers and antipsychotics (for severe symptoms). GHB can be detected in urinary screens but due to its short half life (27min) it is virtually undetectable in urine after 12 hours of ingestion.
  4. Lysergic Acid Diethylamide (LSD): Street names include Acid A, strawberry and microdots. Low doses enhance lights and sounds whereas high doses produce strong emotional and visual effects which might not be always pleasant. Chemically similar to serotonin and effects the dopaminergic, serotoninergic and NMDA receptors, though the exact mechanism is unknown. Presumably increases the glutamate levels in the cortex and causes excitation. LSD has anticholinesterase properties. It causes inhibition of MAO potentiating the effects of endogenous serotonin and histamine. Physical effects include mydriasis, increases wakefulness and reduces apetite. Toxic effects include hypothermia or hyperthermia, tachycardia, frothing and increased blood sugar levels.
  5. Flunitrazepam (Rohypnol): It is a benzodiazepine GABA receptor complex agonist with excellent oral bioavailability and lipohilicity. Street names include Roche, Forget Me Pills, Ropes and Rib. It is abused for its intoxicant and relaxant effects. Availability of this drug is in tablet or capsule form though it can be ground and snorted. It mediates its inhibitory effects by acting on the GABA receptors of brain and spinal cord.17Adverse effects include somnolence, impaired psychomotor behavior, confusion, amnesia, respiratory depression. Chronic use can produce dependence and withdrawl reactions may be present in dependant patients. Acute intoxication requires intravenous flumazenil to reverse the effects. Toxicological tests can detect flunitrazepam in blood and urine upto 72 hours due to quick metabolism and elimination.1
  6. Ketamine: It is a phencyclidine derievative and used as human as well as veterinary anaesthetic. Street names include Special K, Vitamin K, Kit –Kat and cat. It can be taken  can be injected, injected smoked or snorted.The psychedelic effects dissipate in an hour. It is a NMDA receptor antagonist which binds to these receptors decreasing excitatory neurotransmitter release. It also increases dopamine release in the prefrontal cortex and midbrain. Suggested mechanisms also include decrease reuptake of dopamine, serotonin and norepinephrine through unclear mechanisms.18 Acute adverse effects include tachycardia, hypertension, palpitation, respiratory depression, apnoea and unintentional injuries (due to decreased pain sensitivity).Cognitive defects in attention, memory and learning and development of tolerance is seen in chronic abusers. Serious complications include hyperthermia, seizures, rhabdomyolysis and myoglobinuria.
  7. Nitrites (Amyl, Butyl and Isobutyryl): They are available as volatile, clear amber-coloured liquids. They are popular drugs in the rave circuits for their rapid onset of psychoactive and physical effects which include a sense of “high”, slowed sense of time and a carefree sense of physical well being. They are available in glass ampoules which are crushed by fingers and then inhaled. Their effects are apparent in seconds and it dissipates within 3-5 minutes. These drugs are potent vasodilators and were used originally as anti angina drugs. Acute adverse effects include headache, syncope, postural hypotension, increased intraocular pressure and tachycardia. Additional risk of life threatening arrhythmias, loss of consciousness or severe glaucoma exists. A serious complication is methaemoglobinamia which occurs due to oxidation of haemoglobin of red blood cells.

Anaesthetic considerations in rave drug users:-
Anaesthesiologist’s role in face of this menace:

  1. Detect addictive behavior and recognising the clinical effects of these drugs
  2. Safe conduct of anaesthesia in patients with acute toxicity and in chronic abusers.

      3)  Manage rave drug related emergencies
4)  Education and spreading awareness.

Anaesthesiologist can encounter the rave drug abusers in the settings of emergency surgeries (road traffic accidents, physical or sexual assaults) or a variety of elective surgeries. Considering the isolated location of raves, the age group of users, their activities it is likely that the person of this group will be admitted in an emergency situation.

Preoperative Management Strategies:-
History of casual drug abuse if can be elicited beforehand can be of immense help in planning a safe anaesthetic procedure. However identification of potential abusers can be aided by subtle clinical signs during physical examination which can help in raising the clinical degree of suspicion regarding chronic drug usage like:
a) Crusty skin lesions on exposed areas like nose, mouth and lips.
b) Presence of dermatitis or chemical burns (in nitrite users)
c) Coughing, wheezing and dyspnoea ( respiratory irritation of nitrites)
d) Progressive jaundice and weight loss (MDMA induced hepatotoxicity)
e) Hyperpyrexia and dehydration (MDMA induced)
f) Slurred speech, anxiety, agitation, psychotic behavior, emaciated look
History should include whether a single or multiple drugs are abused. Also the route (whether inhalational, intranasal, oral or intravenous) needs to be known. A history of drug abuse is considered as a contraindication to day care surgery. Parturients consuming amphetamine like substances can pose a diagnostic dilemma as hypertension and proteinuria with or without seizures can mimic preeclampsia or eclampsia.19 Local, regional or neuraxial techniques should be considered whenever feasible.20
Baseline investigations as per the clinical situation and type of surgery are needed. However certain investigations are specific to this class of patients:

  1. Serum electrolytes: MDMA users are prone to pronounced hyponatremia. This is due to MDMA induced antidiuretic hormone secretion or excessive water intake to counter dehydration. Serum sodium levels,volume status, urine osmolarity and electrolytes are needed to be assessed. Based on the volume status, hyponatremia correction using normal saline or hypertonic saline should be considered. Hyperkalemia can develop secondary to rhabdomyolysis and precipitate arrhythmias.
  2. Liver function tests : Hepatotoxicity is a known side effect of MDMA and ephedrine use. Patients may present with transaminitis and raised prothrombin time.
  3. Urinanalysis : Can detect presence of myoglobinuria. Rhabdomyolysis (due to hyperthermia, prolonged dancing or seizures) can lead to proteinuria and elevated creatinine kinase levels. This mandates vigorous hydration and forced dieresis with careful attention to fluid, electrolytes and renal status.
  4. Cardiovascular status: Chronic users have a higher baseline pulse rate and blood pressure due to blockade of norepinephrine uptake. Underlying cardiac pathologies like left ventricular hypertrophy (cardiac myocyte hypertrophy), decreased left ventricular compliance due to fibrosis (long term exposure to catecholamines and enhanced collagen), dysrythmias, coronary vasospasm, cardiomyopathies and autonomic dysfunction may coexist. Cardiological assessment is thus helpful to rule out these defects.
  5. Viral markers: High incidence of needle borne infections in these patients who are intravenous drug abusers.

Intraoperative issues in club drug users:-

  1. Preoperative benzodiazepines can help in anxiolysis and increasing seizure thresholds in conscious patients
  2. Establishing venous access may be challenging in intravenous drug users as superficial veins may be thrombosed. It can be fatal in emergency situations where alternative accesses like jugular or intraosseous may need to be considered.
  3. Ketamine as an induction agent is to be avoided as it causes catecholamine release from potentially exhausted stores with unpredictable and undesirable effects.Induction agent like propofol and thiopentone can be used. Etomidate has stable haemodynamic effects but may induce myoclonus and seizures.
  4. Airway concerns exist as bruxism might complicate intubation. In abusers through nasal routes, intranasal intubation can cause septal trauma. Cautious use of succinycholine is advocated to avoid effects like malignant hyperthermia, raising intracranial pressure and worsening hyperkalemia, if present. Effects of succinylcholine can be prolonged due to anticholinesterase inhibition in LSD users. Non depolarisers like rocuronium is helpful as it aids in rapid sequence intubation, slows heat production and maintain paralysis.21 Exaggerated haemodynamic effects and intracranial pressure (ICP) rise can occur following laryngoscopy which needs to be blunted (lignocaine, opioids etc).
  5. Cautious use of volatile anaesthetics intraoperatively to avoid hyperthermia. Narcotic infusion (preferably remifentanyl) lowers surgical stress and reduces the requirement for volatile agents. Minimum alveolar concentration (MAC) of inhalational anaesthetics is increased. Halothane is to be avoided in view of arrhythmias.
  6. Opioid related effects like analgesia and ventilatory depression may be magnified in users of hallucinogens due to their anticholinesterase properties.
  7. Exagerrated effects of anaesthetic drugs may occur due to decreased plasma proteins and fat stores. Anaesthetics metabolized hepatically and renally excreted may have prolonged effects due to fatty liver changes and renal failure (MDMA users).
  8. Intraoperative use of beta blockers can lead to unopposed alpha vasoconstriction leading to hypertension and reflex bradycardia. Labetalol for control of hypertension and tachycardia is suitable for its alpha and beta blocking effects.  Ephedrine for control of hypotension may not be effective due to catecholamine depletion. Phenylephrine (direct acting) and fluid infusions are  required.
  9. Catecholamines (epinephrine, norepinephrine) administration can have exaggerated effects due to reuptake blockade.
  10. Invasive arterial monitoring placed prior to induction helps in early recognition of haemodynamic swings and repeated sampling for electrolytes and blood gases.21
  11. Temperature monitoring is necessary to avoid rhabdomyolysis and DIC. Warming blankets are to be avoided and cold intravenous fluids and ice packs may be necessary to maintain normothermia.
  12. Vigilant monitoring for cardiac dysrythmias (electrolyte disturbances, coronary vasospasm), urine output ( renal failure due to myoglobinuria)
  13. Local anaesthetics (ester type) are metabolized through plasma cholinesterase. Toxicity might result from their use due to inhibition of plasma cholinesterase. Caution should be exercised when using epinephrine containing local anaesthetic solutions. Regional anaesthesia induced hypotension should be treated cautiously with vasoconstrictors to avoid sympathetic hyperactivity.22 Also the altered perception and combative behavior of these patients should be considered.
  14. Universal precautions throughout the conduct of anaesthesia.

 

Post operative concerns:-

  1. Profound neurological changes may occur following recovery from anaesthesia where  preexisting cognitive deficits are amplified.
  2. Motor irritability and hallucinations (flashbacks) may be present during the recovery phase.
  3. Altered pain perception due to changes in µ and κ receptor populations thus prediction of analgesic needs is difficult. Chances of increased use of opioids to obtain chemical gratification. Non opioid analgesics like paracetamol or NSAID’s are encouraged. Regional techniques should be utilized whenever possible.
  4. Deep vein thrombosis (DVT) is common in intravenous drug abusers especially those who use the groin veins.

 

Management of rave drug related emergencies:-
No standard treatment protocol has been identified and supportive care (ACLS protocol) needs to be instituted.23 Medicoegal notification and samples for STD’s, viral markers and toxicological screening should sent immediately. No specific antidote for  rave drugs exist except for flunitrazepam where flumazenil can be helpful in reversing toxicity. Basic management includes cardiac monitoring, pulse oxymetry, urinanalysis and performance of comprehensive chemistry panel to check for electrolytes, renal toxicity and possible underlying disorders. Seizure control (benzodiazepines) maintainence of ventilation and aspiration prophylaxis should be given priority. Gastrointestinal decontamination using activated charcoal and a cathartic should be considered if oral intake was done 60 minutes prior. Severe hypertension can be treated with labetalol, phentolamine or nitroprusside. Hyperthermia should be treated with external and core cooling methods (tepid water bathing, fanning).Serotonin antagonists like cyproheptadine or chlorpromazine can be considered for controlling serotonin syndrome. Methaemoglobinamia causing cyanosis due to nitrites may not respond to oxygen and requires methylene blue.24

Conclusion:-
With the changing societal demographics, rave drugs have emerged as a public menace despite increasing public education and awareness. Anaesthesia providers are likely to encounter such class of patients during preanaesthetic checkups, emergency surgeries or in critical care units. It is imperative that they should be cognizant of the ill effects and potential risks of these drugs. Identification of these patients (through non judgemental enquiry), judicious use of anaesthetic drugs and techniques,  provision of adequate postoperative care and analgesia and following universal precautions forms the mainstay of anaesthetic management of these patients.

 

References:-

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