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Journal of Medicine
Refer to: Klock JC, Boerner U, Becker CE: Coma, hyperthermia
and bleeding associated with massive LSD overdose-A
report of eight cases. West J Med 120:183-188, Mar 1973
TABLE 2.-Toxicologic Data Obtained in Seven caine and two specimens contained small amounts
Patients with Massive LSD Overdose* of ethanol (Table 2).
Blood
Urine Gastric Confiscated Material
Patient Ethanol Cocainet LSD Cocainet LSD
No. (%) (pg/ml) (ng/ml) (0g/ml) (mg/100 ml)
A white flaky material (208 mg) was confis-
1 0 .0 0 NT 0 7.0 cated by police and identified as the large quantity
2 ... 0.08 0 NT 1.3 NT of powder used at the party. Analysis by thin layer
3 0 .0 0 26.0 10.0 NT
4 ...NT NT NT NT 1.2 chromatography, fluorescent analysis, mass spec-
5 ... 0 0 6.6 0 <1mg trography and the melting point and mix melting
6 ... 4 0 11.6 0 NT point identified this substance as almost pure
7 ... 0.02 0 2.1 NT 3.1 (80 to 90 percent) D-lysergic acid diethylamide
*NT = not tested. tartrate.
tMeasured as benzoylecgonine.
Discussion
chromatography according to a modified method Intranasal administration of crushed LSD tablets
of Mul.2 All basic gastric content extracts showed is a common method of administration by LSD
the presence of an ergot alkaloid. By the photo- users when a rapid onset of action is desired. The
degradation method of Andersen3 and using a active use of this route by our patients was cor-
combination of eight reference substances,* this roborated by the onset of symptoms soon after
substance was further characterized as D-lysergic administration of the white powder, the absence
acid diethylamide. The results, shown in Table 2, of LSD in screening samples of food and wine
were confirmed by mass spectrography.t The mass from the party and the. absence of symptoms in
peaks of the isolated material corresponded with members of the party who did not use the powder.
those reported in the literature. and those of The lethal dose of LSD for man is not known, but
authenticated LSD-25, which was used as a con- it ranges from 46 mg per kg in mice8 to 0.3 mg
trol sample. per kg in rabbits8 to 0.1 mg per kg in Asiatic
elephants.9 Interpolated for the body weight of
Urine man, this would result in a lethal dose of 0.2 mg
per kg or an approximate lethal dose of 14,000
Preliminary screening by Mule's2 method of
thin layer chromatography showed possible traces 11g.8 The toxicologic data and the purity of the
powder used by our patients indicate that milli-
of cocaine in some specimens. Therefore, speci- gram amounts of the drug were administered,
mens were rechecked by homogeneous enzyme placing the patients at risk of having severe and
immunoassay4 for benzoylecgonine, the main co- possibly lethal reactions.
caine metabolite in urine.5 Two of the urine speci- LSD is capable of many and varied physiologic,
mens contained small amounts of benzoylecgonine psychologic and biochemical effects.8'10"11 Most of
(Table 2). these effects are thought to be due to LSD's ability
to affect 5-hydroxytryptamine receptors both cen-
Blood trally and peripherally'2-'4 and to its generalized
Blood was analyzed for LSD by the back extrac- stimulation of the reticulocortical system.8 The
tion method of Aghajanian and Bing, and the previously observed physiologic manifestations of
results were compared with standards of serum psychosis, hyperexcitability, tachycardia, mydri-
containing 5, 10, 20 and 40 nanograms (ng) LSD asis8" 5"16 and hyperthermia'7 were prominent in
per ml. All specimens analyzed contained LSD our patients, but the degree of central nervous
(Table 2). Blood was analyzed for cocaine, using system depression and respiratory inhibition that
the same general method as for urine, and for occurred in these patients has only been demon-
ethanol and other volatile substances, using gas strated in animals given very large doses.8 Further-
chromatography.7 No specimen contained co- more, the generalized bleeding problem observed
*D-lysergic acid diethylamide tartrate (LSD-25@, Sandoz), er- in four of our patients has not been described
gotamine tartrate (Sandoz), methysergid(e) maleate (Sansert(,
Sandoz), methylergonovine maleate (Methergine, Sandoz), er-
before with LSD. The clinical and laboratory data
gonovine maleate (Ergotrate maleate, Lilly), dihydroergotamine
(methanesulfonate) (DHE-45, Sandoz), D-lysergamide tartrate
suggest that platelet function was abnormal. Little
(ergine), D-iso-lysergamide tartrate (iso-ergine tartrate). literature on LSD and platelet function is avail-
tVarian NAT-GNOME quadropol mass spectrograph, Varian Asso- able. However, Michal'8 showed that LSD-25 in 1
ciates, Palo Alto, California.
to 3 nanomolar concentrations could significantly She remained comatose and continued to bleed
inhibit 5--hydroxytryptamine-induced platelet ag- at the site of insertion of the endotracheal tube
gregation in vitro; no effect on adenosine diphos- and in the urine. After 5 hours, the fever, coma
phate-induced aggregation was noted. Cocaine and bleeding gradually resolved. The patient was
also affects platelet function in vitro in much fully awake by the 12th hour, was able to walk
larger concentration.'9'20 Our analytical data do after removal of the tube and was discharged on
not indicate that cocaine played a significant role the second hospital day.
in these cases, making the possibility of cocaine- PATIENT 2. A 19-year-old woman arrived at
induced platelet dysfunction unlikely. However, the hospital in an extremely lethargic state, re-
more evidence is needed before LSD can be impli- sponding only to very painful stimuli. Within 10
cated as the cause of the bleeding in these patients. minutes she became severely agitated, spontane-
Treatment of our patients was entirely sup- ously flailing her arms and legs and continuously
portive and recovery was relatively rapid. Some of screaming. The pupils were dilated and unrespon-
them were able to converse after 4 to 5 hours and sive to light. There was no nuchal rigidity. The
all were normal within 12 hours. Most did not re- bowel sounds were hyperactive, stools were
member being brought to the hospital; otherwise, formed and greenish, and the nasogastric aspirate
no apparent psychologic or physical ill effects contained small amounts of blood mixed with
were noted in a year of follow-up examinations food. Blood oozed from venipuncture sites and
of five patients. Most of the patients continue to large bruises formed at sites of trauma. Hemo-
use LSD intermittently. Death from LSD overdose globin was 14 grams per dL, packed cell volume
still has not been confirmed toxicologically; never- 40.8 percent, platelets 186,000 per IAL, and leu-
theless, the rapid administration of large doses kocytes 21,500 per /.L with 80 percent neutro-
of LSD in man is associated with striking and dis- phils, 19 percent lymphocytes and 1 percent
tinctive clinical manifestations and is life-threat- monocytes. Prothrombin time was 12.5 seconds,
ening. partial thromboplastin time 27.3 seconds. Glucose
was 180 mg, creatinine 1.5 mg and blood urea
APPENDIX nitrogen 20 mg per dL. Serum sodium was 142
mEq, potassium 4.0 mEq, chloride 110 mEq, and
PATIENT 1. A 20-year-old woman was coma- bicarbonate 25 mEq per liter. There was a 4 plus
tose and unresponsive to pain with vomitus in the reaction for blood in the urine, and the stool
mouth and hypopharynx on arrival at San Fran- guaiac test reaction was 2 plus. An electrocardio-
cisco General Hospital. Breathing was shallow, gram showed sinus tachycardia.
irregular and ineffective; the pupils were dilated Diazepam, 10 mg, was administered intraven-
and unreactive. There were hyperactive bowel ously and the patient was packed in ice bags. She
sounds, but no diarrhea. Bleeding at venipuncture began to have many watery greenish stools. She
sites persisted for more than 20 minutes. The was placed in a quiet dark room and became
hemoglobin was 13.9 grams per deciliter (dL), quieter. Over the next hour she became gradually
packed cell volume 43.2 percent, platelets 245,000 less responsive and finally only responded to deep
per microliter (MtL), and white blood cell count pain. The arterial blood pO2 was 56 mm of mer-
19,000 per /uL with 35 percent segmented neu- cury, pCO, 46 mm of mercury, and pH 7.28.
trophils, 2 percent eosinophils, 1 percent baso- Respiratory arrest necessitated intubation and
phils, and 62 percent lymphocytes. On urinalysis respiratory assistance for 4 hours at which time
there was a 2 plus reaction for blood. The blood she began to regain consciousness. Within the next
urea nitrogen was 9 mg and creatinine 0.7 mg per 8 hours the patient recovered fully and was dis-
dL, serum sodium was 140 mEq, potassium 4.4 charged the following day.
mEq, chloride 108 mEq and bicarbonate 25 mEq PATIENT 3. A 28-year-old woman arrived at
per liter, glucose was 1 15 mg per dL, prothrombin the hosiptal vomiting and unable to speak, had an
time 12.4 seconds and partial thromboplastin expressionless stare and was unresponsive even
time 24.5 seconds. Both the stool and vomitus to severe pain. The pupils were dilated and fixed
were 3 plus reactive for blood. and the reflexes were hyperactive. She did not
The patient was supported by artificial ventila- have diarrhea. The hemoglobin was 14.5 grams
tion via endotracheal tube and was placed on a per dL, packed cell volume 41.2 percent and leu-
hypothermic blanket and given intravenous fluids. kocytes 23,200 per IAL with 67 percent neutro-
phils, 1 percent basophils, 36 percent lympho- rhage or diarrhea. The hemoglobin was 15.7
cytes and 6 percent monocytes. The platelets were grams per dL, packed cell volume 46 percent,
normal on a blood smear. The prothrombin time platelet count 294,000 per ,uL and leukocytes
was 11.9 seconds, partial thromboplastin time 17,500 per tL with 39 percent neutrophils, 54
38.7 seconds and blood glucose 105 mg per dL. percent lymphocytes, 1 percent eosinophils and
The vomitus was positive for blood. 6 percent monocytes. Blood urea nitrogen was 22
Dextrose and saline solution were administered mg and creatinine 1.4 mg per dL. Serum sodium
intravenously. The patient gradually became more was 141 mEq, potassium 3.5 mEq, chloride 109
responsive. Except for three episodes of brown mEq and bicarbonate 20 mEq per liter. Arterial
watery diarrhea and transient writhing dystonic blood p2 was 52 mm of mercury, pCO2 46 mm
movements, the course of recovery was unevent- of mercury, and pH 7.25. Urinalysis showed a 1
ful. The patient was completely normal after 12 plus reaction for ketones and a 3 plus reaction for
hours and was discharged on the second hospital blood. The vomitus was positive for blood.
day. After 30 minutes it was easier to arouse the
PATIENT 4. A 33-year-old woman arrived at patient from coma. He was increasingly psychotic
the hospital unconscious and unresponsive to and had severe visual hallucinations. However,
painful stimuli. She had frothy sputum and vom- during the next 4 hours he became sleepy and less
itus in the mouth, nose and hypopharynx. The agitated. He gradually recovered and left the
vomitus contained small flecks of blood. The pu- hospital against medical advice 12 hours after
pils were dilated and unresponsive to light. The admission.
bowel sounds were hyperactive but there was no PATIENT 6. A 29-year-old man was unrespon-
diarrhea. The hemoglobin was 13.0 grams per dL, sive on arrival at the hospital. Except for blood
packed cell volume 38.8 percent and white blood pressure of 230/130 mm of mercury, dilated
cell count 22,300 per ,wL with a normal differen- pupils and diaphoresis, the results of physical ex-
tial. Urinalysis showed a 4 plus reaction for glu- amination were within normal limits. There was
cose and blood. Blood glucose was 204 mg, no evidence of bleeding. The hemoglobin was
creatinine 0.7 mg and urea nitrogen 11 mg per 16.4 grams per dL, packed cell volume 46.7 vols
dL. Serum sodium was 141 mEq, potassium 3.7 percent and leukocytes 17,900 per 1tL with a nor-
mEq, chloride 103 mEq and bicarbonate 28 mEq mal differential count. The platelets were normal
per liter. The plasma prothrombin time was 11.6 on smear and the prothrombin time was 12.5
seconds and partial thromboplastin time 19.3 seconds. Blood glucose was 142 mg, blood urea
seconds. The platelets were normal on a blood nitrogen 19 mg and creatinine 0.8 mg per dL.
smear. Arterial PO2 was 104 mm of mercury, pCO2 was
The patient vomited in the emergency room, 28 mm of mercury, and pH was 7.41. The vom-
aspirated vomitus and became apneic. Endotra- itus was positive for blood.
cheal intubation and artificial ventilation were After 40 minutes the patient had gradually be-
instituted and hydrocortisone, 500 mg, and peni- come more responsive though he was grossly psy-
cillin, 6 million units, were administered intra- chotic, screamed loudly and had severe visual hal-
venously. Blood oozed at venipuncture sites and lucinations. The blood pressure gradually fell to
at the site of insertion of the endotracheal tube. 170/110 mm of mercury over an hour and was
Artificial ventilation was maintained for 2 hours 130/70 3 hours after admission. The patient re-
and then terminated when the patient began covered without complication over the next 8
thrashing about. Bleeding continued for several hours and left the hospital the following day.
hours and the tube was removed approximately 8 PATIENT 7. A 28-year-old man walked into
hours after insertion. She made an uneventful the emergency room stating that he thought he
recovery and left the hospital on the third hos- had been poisoned. He was belligerent and was
pital day. having visual hallucinations. Physical examina-
PATIENT 5. A 39-year-old man arrived at the tion showed no abnormalities with no evidence of
hospital unconscious and unresponsive to pain. diarrhea or bleeding; however, he subsequently
He had no gag reflex while vomitus was being vomited material containing blood. The hemo-
suctioned from his mouth and hypopharynx. He globin was 16.3 grams per dL, packed cell volume
was diaphoretic with widely dilated pupils and 47.2 percent and white blood cell count 13,500
hyperactive bowel sounds but there was no hemor- per AL with 66 percent neutrophils, 3 percent