The perfect crime

A 27 year old woman presented to the emergency department with collapse, left sided weakness and loss of sensation, and amnesia. We got a history of the night's events before admission from her friends. She had no past medical history and was not known to be a recreational drug user.

On a night out to a club, she had consumed half a bottle of wine, two pints of Guinness, and five single measures of spirits. However, she was "not that drunk and quite alert." After leaving for the toilet alone, she was later found sitting on a chair at the bar with her head on the tabletop. She seemed confused and did not recognise anyone. Her friends became concerned because she was difficult to arouse. They carried her outside and called an ambulance. She then passed out and became unresponsive for several minutes, but had no seizures, no abnormal movements, no incontinence, and did not bite her tongue.

She could not recognise her friends, did not know her own name, date of birth, or occupation. Nor could she remember her parents' names. However, she could recall her sister's name and occupation and a brother who apparently died some years ago in a road crash. She also remembered accepting a glass of orange juice from a stranger called James and going to the toilet, collapsing, and hitting the back of her head. She then remembered that James asked for her mobile phone to call a friend. She thinks she gave this to him. He then asked for credit cards and asked her to go with him. She is not sure if she complied and does not remember how she ended up on a stool by the bar.

On examination she was talking and opening her eyes spontaneously but was confused, disorientated, and distressed about her amnesia. She could move all limbs, but her right side moved more than her left. Her pulse rate was 86 regular, blood pressure was 122/79 which reduced to 90/50 four hours after admission. Her respiratory rate was 16 and she was apyrexial.

Neurological examination showed that her cranial nerves were normal apart from a left sided visual inattention. Power was moderately impaired in the left upper and lower limbs associated with a left sided tactile inattention. Reflexes were slightly reduced on the left side and plantar reflexes went down.

Questions

(1) What is the differential diagnosis?

(2) What do you think the diagnosis was?

(3) What investigations would you do?

(4) What do you do next?

(5) How would this patient be managed subsequently and what advice would you give to the patient?

Answers

(1) Alcohol intoxication, drugs, stroke, subarachnoid haemorrhage, meningitis.

(2) She had drunk a drink spiked with flunitrazepam (Rohypnol).

(3) Alcohol concentrations, computed tomography scan, drug screen, full blood count, urea and electrolytes, C reactive protein, thyroid function tests, arterial blood gases, mid-stream urine sample and dipstick, urine toxicology. In this case, there was no evidence of drug poisoning--this is not unusual in such cases. Consult an expert in sexual assault to ascertain whether a sexual crime has taken place.

(4) Most patients with poisoning require only general care and vital system support. Simple observations--level of consciousness (Glasgow coma scale), pulse oximetry to measure oxygen saturation, blood pressure and pulse rate, pupil size and reaction to light, and temperature.

(5) Subsequent management was supportive. She was discharged two days later and advised:

• To take a week off work
• Not to drive until she has been seen in outpatients a week later
• To be careful when operating machinery and heating devices
• To ask her family to look after her for the next few days
• That a criminal offence had occurred and she should contact the police should she wish to take it further.

JOSH SHER/SPL

Discussion

Flunitrazepam (Rohypnol), a benzodiazepine, is a class C drug if possessed illegally--without prescription. People use it to incapacitate victims and prevent them from resisting sexual assault or other crimes, by spiking their drink.^{1 2} Other substances used this way include * hydroxybutyrate (GHB) (made illegal in the United Kingdom in July 2003), hyoscine, burundanga, and ketamine. In general, criminals prefer drugs which enter the brain rapidly to those which are absorbed more slowly.³

Common street names

Rophies, roofies, R2, roofenol, Roche, roachies, la rocha, rope, rib, circles, Mexican valium, roach 2, roopies, ropies, rophies, stupefi, ruffies, getting roached, lunch money drug, Pingus, Reynolds, Robutal, Row-shay, Wolfies, and the forget me pill

JOSH SHER/SPL

Pharmacological effects

Flunitrazepam is used for its sedative-hypnotic properties. It reduces activity and excitement calming the recipient and producing drowsiness and sleep.^{2 4} Doctors prescribe it as a presurgical sedative and for insomnia. Loss of memory for unpleasant events is a welcome effect in these circumstances.⁵ The amnesia it causes results from a lack of concentration and attention and is typified by a deficit in "episodic" memory--remembrance of recent events, the circumstances in which they occurred, and their sequence in time. This occurs by altering the rate of peptide chain formation of certain neurones.⁶ Impairment of episodic memory may occasionally lead to memory lapses or blackouts.¹ By contrast, other memory functions--memory for words, ability to remember a telephone number for a few seconds, and recall of long term memories--are not impaired.

Criminals exploit these effects on their unsuspecting victims. Other central nervous system depressants--for example, alcohol--can potentate the effects of flunitrazepam. This could potentially have been fatal even though benzodiazepines are relatively safe in overdose.

Flunitrazepam acts selectively at GABA_A receptors and exerts an extra-inhibitory influence on neurones, blocking the arousal of higher brain centres. The high affinity and effectiveness of flunitrazepam combine to make it one of the most potent of the benzodiazepines. Because of the inhibitory activity, the brain's output of excitatory neurotransmitters is reduced. These are necessary for normal alertness, memory, muscle tone, and coordination, emotional responses, endocrine gland secretions, heart rate and blood pressure control, and a host of other functions, all of which may be impaired by flunitrazepam.

Flunitrazepam is odourless, colourless, and tasteless and can dissolve in most types of drinks. It is readily absorbed from the gastrointestinal tract. The elimination half life is about 18-26 hours but varies between individuals and the half life of active metabolites is 20-200 hours.^{5 6} It is 10 times more potent than diazepam and is soluble in lipids, which contributes to its rapid uptake into brain tissue and fast onset of central effect 30 minutes after ingestion. Effects peak within two hours and may persist for up to eight hours or more depending upon the dosage and may not fully wear off for several days and may continue to exert subtle effects within the body.⁵

Flunitrazepam is metabolised by liver enzymes. Accumulation of the breakdown products in the patient would have contributed to the prolonged effects of the drug.⁶ These metabolites are inactivated by glucuronidation and excreted mainly by the kidneys.⁷

Management

Many drugs--especially alcohol--have been used throughout history to reduce sexual inhibitions, to induce sexual cooperation, and to facilitate sexual assault.^{4 8} Flunitrazepam produces symptoms similar to alcohol intoxication and its use should be suspected in any sexual assault involving a person who appears intoxicated or has amnesia. Doctors should collect a urine specimen to analyse for metabolites. Gas chromatography of the urine sample can detect metabolites up to 72 hours after ingestion of 2 mg of flunitrazepam.⁶ However, few perpetrators of such crimes have been convicted in which toxicology evidence has established that flunitrazepam was actually involved. This does not reduce the concern that flunitrazepam may be used for this purpose.³

Impairment of consciousness is treated conventionally, paying particular attention to maintenance of the airway. Doctors can use the specific benzodiazepine antagonist flumazenil or activated charcoal to reverse coma induced by flunitrazepam.⁸ However, flumazenil is not used in most cases. The patient is given supportive care and doctors should observe the patient for at least six hours after ingestion and at least 24 hours if the patient is still symptomatic after six hours.

In 1995, flunitrazepam became the first benzodiazepine to require more rigid controls and was moved to Schedule III by the World Health Organization, requiring more thorough record keeping on its distribution.³ In 1997, Hoffman-LaRoche announced a reformulation of Rohypnol. The new tablet releases a blue dye when dissolved in liquid. However, the reformulated drug cannot be distributed until it is reviewed in every country in which it is marketed. The blue dye is difficult to see in dark drinks or when in a dark setting such as a dimly lit bar. The old drug still remains on the market at this time.

Jalil Ahmed fourth year medical student, University of Manchester

C M Cheshire consultant general physician, Manchester Royal Infirmary


studentBMJ 2004;12:177-220 May ISSN 0966-6494

1. Ashton H. Toxicity and adverse consequences of benzodiazepine use. Psychiatr Ann 1995;25:158-65.
2. Parrott A. State of the art: psychoactive drugs of use and abuse: wobble, rave, inhale or crave? J Clin Psychopharmacol 1995;9:390-1.
3. Woods J H, Winger G. Abuse liability of flunitrazepam. J Clin Psychopharmacol 1997;17(3 suppl 2):S1-57.
4. Schwartz R H, Milteer R, LeBeau M A. Drug-facilitated sexual assault ("date rape"). Southern Med J 2000;93:558-61.
5. Ashton H. Benzodiazepine abuse, drugs and dependence. London, New York: Harwood Academic Publishers Routledge, 2002:197-212.
6. Labianca DA. Rohypnol: profile of the "date-rape drug." http://colossus.chem.umass.edu/genchem/chem102/Articles/drape.
   htm (accessed 7 Apr 2004).
7. Mattila M A K, Larni H M. Flunitrazepam: a review of its pharmacological properties and therapeutic use. Drugs 1980;20:353-74.
8. Schwartz R H, Weaver A B. Rohypnol, the date rape drug. Clin Pediatr 1998;37:321.

       

           

Responses published this month Articles Responses EDUCATION The perfect crime       Jalil Ahmed (May 2004) S A S Price (May 7, 2004) Read this response EDUCATION The perfect crime       Jalil Ahmed (May 2004) S A S Price (May 7, 2004)       SHO orthopaedics Hull Royal Infirmarysas_price@hotmail.com Thankyou for your article on a patient with neurological symptoms following a "spiked" drink. It is not uncommon to see such patients in the A&E department, with a history of possible intoxication from unknown substance. Assessing these patients should be approached in the same way as any other emergency; that is, according to ALS guidelines. Initially ABC (airway, breathing, circulation) should be assessed, however rapidly, followed by D and E (disability and exposure). Many instructors will suggest ABCDEFG: ABC Don't Ever Forget Glucose. Clearly in the instance reported, a very early investigation should be a capillary glucose (BM). Alcohol and other drugs can cause hypoglycaemia which (as with severe hyperglycaemia) could present with all of the neurological symptoms reported. In patients presenting with alcohol and drug intoxications, it is easy to attribute symptoms to these and to neglect to look for hypo/hyperglycaemia or head injury. These can deteriorate rapidly and irreversibly if missed early on. So when assessing an intoxicated patient/collapse query cause/comatose patient ABC DE and don't ever forget glucose.