THE WESTERNJournal of Medicine

Refer to: Klock JC, Boerner U, Becker CE: Coma, hyperthermiaand bleeding associated with massive LSD overdose-Areport of eight cases. West J Med 120:183-188, Mar 1973

Eight patients were seen within 15minutes of intranasal self-admin-istration of large amounts of pureD-lysergic acid diethylamide (LSD)tartrate powder. Emesis andcollapse occurred along withsigns of sympathetic overactivity,hyperthermia, coma and respi-ratory arrest. Mild generalizedbleeding occurred in severalpatients and evidence of plateletdysfunction was present in all.Serum and gastric concentrationsof LSD tartrate ranged from 2.1to 26 nanograms per ml and 1,000to 7,000 ,g per 100 ml, respec-tively. With supportive care, allpatients recovered. Massive LSDoverdose in man is life-threaten-ing and produces striking anddistinctive manifestations.

ALTHOUGH THERE HAVE BEEN many reports ofover-dose with D-lysergic acid diethylamide (LSD)in man, little toxicologic data are available. Thephysiologic effects of LSD in doses greater than 1mg have not been studied in man and the lethaldose must be interpolated from animal studies.We performed extensive toxicologic studies oneight people who took large doses of LSD; the re-sults and clinical-toxicologic correlations are re-ported herein.From the Division of Clinical Pharmacology, the Toxicology

Laboratory, and the Medical Service, San Francisco GeneralHospital, and the Department of Medicine, University of Cali-fornia, San Francisco.

Presented by invitation at the American Academy of ClinicalToxicology Meeting, San Diego, California, August 2, 1973.

Submitted August 30, 1973.Reprint requests to: J. C. Klock, MD, Department of Medicine,

Division of Hematology, Room 506 M, University of California,San Francisco, San Francisco, CA 94143.

Coma, Hyperthermiaand BleedingAssociated withMassiveLSD OverdoseA Report of Eight Cases

JOHN C. KLOCK, MDUDO BOERNER, MSCHARLES E. BECKER, MDSan Francisco

Reports of CasesOn 29 July 1972, four women and four men

ranging in age from 19 to 39 years were admittedto the emergency room at San Francisco GeneralHospital for drug overdose. Following a dinnerparty, they had "snorted" (inhaled through astraw placed in one nostril) a small amount ofcocaine and a quantity of white powder believedto be cocaine. All eight were reported to havesnorted at least two "lines" (rows of powder meas-uring approximately 3 x 4 X 30 mm) of the secondsubstance. Within 5 minutes they experiencedanxiety, restlessness, generalized parasthesias andmuscle discomfort, vomiting and physical col-lapse. Ten minutes later they were admitted to theemergency room in varying degrees of intoxica-tion (Table 1 and Appendix).THE WESTERN JOURNAL OF MEDICINE 183

LSD OVERDOSE

TABLE 1.-Clinical Manifestations of Massive LSD Overdose in Eight PatientsBlood

Patient Pressure Respirations Pulse Temperature PupilsNo. Age, Sex (mm Hg) (breaths/min) (beats/min) (OF) (mm) Bleeding Other1 . 209 130/90 6 120 104.0 8 + Coma, respiratory

arrest2.199 130/30 33 200 107.0 7 + Coma, respiratory

arrest, diarrhea3 ..... 289 160/60 24 150 99.5 8 - Writhing and dystonic

movements, diarrhea4 ..... 339 110/70 9 110 98.0 8 + Coma, respiratory

arrest, aspiration5.395 130/80 20 120 100.8 7 - Coma, aspiration6.29a 230/130 30 112 98.8 6 - Coma, aspiration7 . 285a 130/80 20 170 98.6 6 - Hyperactive, psychotic,

hallucinating8.28a 190/95 20 120 102.4 7 + Hyperactive, psychotic,

hallucinating

Figure 1.-Gross appearance of the blood clot fromPatient 1 and a normal control clot (left) and resultsof autologous serum incubation at 370C for 6 hours ofclots from Patient 1 and a normal control clot (right).The normal control specimen is to the right in eachpicture.

Five were comatose when first seen and most

were extremely hyperactive with severe visual andauditory hallucinations at some point during theircourse. Three required endotracheal intubationand assisted ventilation and three aspirated vom-itus. All had sinus tachycardia, widely dilated andfixed pupils, emesis, flushing and sweating. Feverdeveloped in four and diarrhea in two. Transient

hypertension was present in three patients and nopatient had convulsions. All had coagulopathy asmanifested by the inability to form firm clots and

absence of clot retraction in the blood specimentubes. Seven had guaiac-positive vomitus and fourshowed exidence of mild generalized bleeding(microscopic hematuria in two, gross hematuriain two, oozing at venipuncture sites in three andsmall amounts of blood in the vomitus or stool inall four patients).

Laboratory data showed normal or negativevalues (see Appendix) for the following: bloodglucose and serum sodium, potassium, and bicar-bonate levels, hemoglobin (13.0 to 16.4 gramsper deciliter), platelet count (186,000 to 458,000per microliter), prothrombin time (11.0 to 12.5seconds) and partial thromboplastin time (19.3to 38.7 seconds), chest roentgenograms and elec-trocardiograms. Results of liver and renal func-tion tests were within normal limits in the threepatients studied. Direct examination of the bloodclots and results of clot retraction tests on severalpatients showed friable clots that fell apart easilywithout dissection, and absence of clot retraction(Figure 1). Supportive care included respiratoryassistance, use of hypothermic blankets, and ad-ministration of antibiotics and corticosteroidswhen indicated. Bleeding was mild and disap-peared within 4 to 6 hours. Blood transfusionswere unnecessary and all patients recovered com-pletely within 12 hours. All were discharged orleft the hospital within 48 hours of admission. Noresidua were observed in a year of direct follow-up of five patients.

Toxicologic DataSpecimens of blood, urine and gastric contents

were obtained on admission from seven patientsand analyses were performed as follows.

Gastric ContentExtraction of the gastric contents for toxico-

logic screening was performed according to themethod of Sunshine' and analyzed by thin layer

184 MARCH 1974 * 120 * 3

LSD OVERDOSE

TABLE 2.-Toxicologic Data Obtained in SevenPatients with Massive LSD Overdose*

BloodUrine Gastric

Patient Ethanol Cocainet LSD Cocainet LSDNo. (%) (pg/ml) (ng/ml) (0g/ml) (mg/100 ml)1 0 .0 0 NT 0 7.02 ... 0.08 0 NT 1.3 NT3 0 .0 0 26.0 10.0 NT4 ...NT NT NT NT 1.25 ...0 0 6.6 0

LSD OVERDOSE

to 3 nanomolar concentrations could significantlyinhibit 5--hydroxytryptamine-induced platelet ag-gregation in vitro; no effect on adenosine diphos-phate-induced aggregation was noted. Cocainealso affects platelet function in vitro in muchlarger concentration.'9'20 Our analytical data donot indicate that cocaine played a significant rolein these cases, making the possibility of cocaine-induced platelet dysfunction unlikely. However,more evidence is needed before LSD can be impli-cated as the cause of the bleeding in these patients.

Treatment of our patients was entirely sup-portive and recovery was relatively rapid. Some ofthem were able to converse after 4 to 5 hours andall were normal within 12 hours. Most did not re-member being brought to the hospital; otherwise,no apparent psychologic or physical ill effectswere noted in a year of follow-up examinationsof five patients. Most of the patients continue touse LSD intermittently. Death from LSD overdosestill has not been confirmed toxicologically; never-theless, the rapid administration of large dosesof LSD in man is associated with striking and dis-tinctive clinical manifestations and is life-threat-ening.

APPENDIX

PATIENT 1. A 20-year-old woman was coma-tose and unresponsive to pain with vomitus in themouth and hypopharynx on arrival at San Fran-cisco General Hospital. Breathing was shallow,irregular and ineffective; the pupils were dilatedand unreactive. There were hyperactive bowelsounds, but no diarrhea. Bleeding at venipuncturesites persisted for more than 20 minutes. Thehemoglobin was 13.9 grams per deciliter (dL),packed cell volume 43.2 percent, platelets 245,000per microliter (MtL), and white blood cell count19,000 per /uL with 35 percent segmented neu-trophils, 2 percent eosinophils, 1 percent baso-phils, and 62 percent lymphocytes. On urinalysisthere was a 2 plus reaction for blood. The bloodurea nitrogen was 9 mg and creatinine 0.7 mg perdL, serum sodium was 140 mEq, potassium 4.4mEq, chloride 108 mEq and bicarbonate 25 mEqper liter, glucose was 1 15 mg per dL, prothrombintime 12.4 seconds and partial thromboplastintime 24.5 seconds. Both the stool and vomituswere 3 plus reactive for blood.The patient was supported by artificial ventila-

tion via endotracheal tube and was placed on ahypothermic blanket and given intravenous fluids.

She remained comatose and continued to bleedat the site of insertion of the endotracheal tubeand in the urine. After 5 hours, the fever, comaand bleeding gradually resolved. The patient wasfully awake by the 12th hour, was able to walkafter removal of the tube and was discharged onthe second hospital day.

PATIENT 2. A 19-year-old woman arrived atthe hospital in an extremely lethargic state, re-sponding only to very painful stimuli. Within 10minutes she became severely agitated, spontane-ously flailing her arms and legs and continuouslyscreaming. The pupils were dilated and unrespon-sive to light. There was no nuchal rigidity. Thebowel sounds were hyperactive, stools wereformed and greenish, and the nasogastric aspiratecontained small amounts of blood mixed withfood. Blood oozed from venipuncture sites andlarge bruises formed at sites of trauma. Hemo-globin was 14 grams per dL, packed cell volume40.8 percent, platelets 186,000 per IAL, and leu-kocytes 21,500 per /.L with 80 percent neutro-phils, 19 percent lymphocytes and 1 percentmonocytes. Prothrombin time was 12.5 seconds,partial thromboplastin time 27.3 seconds. Glucosewas 180 mg, creatinine 1.5 mg and blood ureanitrogen 20 mg per dL. Serum sodium was 142mEq, potassium 4.0 mEq, chloride 110 mEq, andbicarbonate 25 mEq per liter. There was a 4 plusreaction for blood in the urine, and the stoolguaiac test reaction was 2 plus. An electrocardio-gram showed sinus tachycardia.

Diazepam, 10 mg, was administered intraven-ously and the patient was packed in ice bags. Shebegan to have many watery greenish stools. Shewas placed in a quiet dark room and becamequieter. Over the next hour she became graduallyless responsive and finally only responded to deeppain. The arterial blood pO2 was 56 mm of mer-cury, pCO, 46 mm of mercury, and pH 7.28.Respiratory arrest necessitated intubation andrespiratory assistance for 4 hours at which timeshe began to regain consciousness. Within the next8 hours the patient recovered fully and was dis-charged the following day.

PATIENT 3. A 28-year-old woman arrived atthe hosiptal vomiting and unable to speak, had anexpressionless stare and was unresponsive evento severe pain. The pupils were dilated and fixedand the reflexes were hyperactive. She did nothave diarrhea. The hemoglobin was 14.5 gramsper dL, packed cell volume 41.2 percent and leu-kocytes 23,200 per IAL with 67 percent neutro-

186 MARCH 1974 * 120 * 3

LSD OVERDOSE

phils, 1 percent basophils, 36 percent lympho-cytes and 6 percent monocytes. The platelets werenormal on a blood smear. The prothrombin timewas 11.9 seconds, partial thromboplastin time38.7 seconds and blood glucose 105 mg per dL.The vomitus was positive for blood.

Dextrose and saline solution were administeredintravenously. The patient gradually became moreresponsive. Except for three episodes of brownwatery diarrhea and transient writhing dystonicmovements, the course of recovery was unevent-ful. The patient was completely normal after 12hours and was discharged on the second hospitalday.

PATIENT 4. A 33-year-old woman arrived atthe hospital unconscious and unresponsive topainful stimuli. She had frothy sputum and vom-itus in the mouth, nose and hypopharynx. Thevomitus contained small flecks of blood. The pu-pils were dilated and unresponsive to light. Thebowel sounds were hyperactive but there was nodiarrhea. The hemoglobin was 13.0 grams per dL,packed cell volume 38.8 percent and white bloodcell count 22,300 per ,wL with a normal differen-tial. Urinalysis showed a 4 plus reaction for glu-cose and blood. Blood glucose was 204 mg,creatinine 0.7 mg and urea nitrogen 11 mg perdL. Serum sodium was 141 mEq, potassium 3.7mEq, chloride 103 mEq and bicarbonate 28 mEqper liter. The plasma prothrombin time was 11.6seconds and partial thromboplastin time 19.3seconds. The platelets were normal on a bloodsmear.

The patient vomited in the emergency room,aspirated vomitus and became apneic. Endotra-cheal intubation and artificial ventilation wereinstituted and hydrocortisone, 500 mg, and peni-cillin, 6 million units, were administered intra-venously. Blood oozed at venipuncture sites andat the site of insertion of the endotracheal tube.Artificial ventilation was maintained for 2 hoursand then terminated when the patient beganthrashing about. Bleeding continued for severalhours and the tube was removed approximately 8hours after insertion. She made an uneventfulrecovery and left the hospital on the third hos-pital day.

PATIENT 5. A 39-year-old man arrived at thehospital unconscious and unresponsive to pain.He had no gag reflex while vomitus was beingsuctioned from his mouth and hypopharynx. Hewas diaphoretic with widely dilated pupils andhyperactive bowel sounds but there was no hemor-

rhage or diarrhea. The hemoglobin was 15.7grams per dL, packed cell volume 46 percent,platelet count 294,000 per ,uL and leukocytes17,500 per tL with 39 percent neutrophils, 54percent lymphocytes, 1 percent eosinophils and6 percent monocytes. Blood urea nitrogen was 22mg and creatinine 1.4 mg per dL. Serum sodiumwas 141 mEq, potassium 3.5 mEq, chloride 109mEq and bicarbonate 20 mEq per liter. Arterialblood p2 was 52 mm of mercury, pCO2 46 mmof mercury, and pH 7.25. Urinalysis showed a 1plus reaction for ketones and a 3 plus reaction forblood. The vomitus was positive for blood.

After 30 minutes it was easier to arouse thepatient from coma. He was increasingly psychoticand had severe visual hallucinations. However,during the next 4 hours he became sleepy and lessagitated. He gradually recovered and left thehospital against medical advice 12 hours afteradmission.

PATIENT 6. A 29-year-old man was unrespon-sive on arrival at the hospital. Except for bloodpressure of 230/130 mm of mercury, dilatedpupils and diaphoresis, the results of physical ex-amination were within normal limits. There wasno evidence of bleeding. The hemoglobin was16.4 grams per dL, packed cell volume 46.7 volspercent and leukocytes 17,900 per 1tL with a nor-mal differential count. The platelets were normalon smear and the prothrombin time was 12.5seconds. Blood glucose was 142 mg, blood ureanitrogen 19 mg and creatinine 0.8 mg per dL.Arterial PO2 was 104 mm of mercury, pCO2 was28 mm of mercury, and pH was 7.41. The vom-itus was positive for blood.

After 40 minutes the patient had gradually be-come more responsive though he was grossly psy-chotic, screamed loudly and had severe visual hal-lucinations. The blood pressure gradually fell to170/110 mm of mercury over an hour and was130/70 3 hours after admission. The patient re-covered without complication over the next 8hours and left the hospital the following day.

PATIENT 7. A 28-year-old man walked intothe emergency room stating that he thought hehad been poisoned. He was belligerent and washaving visual hallucinations. Physical examina-tion showed no abnormalities with no evidence ofdiarrhea or bleeding; however, he subsequentlyvomited material containing blood. The hemo-globin was 16.3 grams per dL, packed cell volume47.2 percent and white blood cell count 13,500per AL with 66 percent neutrophils, 3 percent

THE WESTERN JOURNAL OF MEDICINE 187

LSD OVERDOSE

basophils, 21 percent lymphocytes and 10 per-cent monocytes. The platelet count was 458,000per ,uL, the prothrombin time was 11.0 secondsand partial thromboplastin time 34.6 seconds.Serum sodium was 140 mEq, potassium 4.3 mEq,chloride 101 mEq, bicarbonate 24 mEq andcreatinine 1.4 mEq per liter. Protein was 7.6grams, albumin 4.6 grams and bilirubin 0.3 mgper dL. Lactic dehydrogenase was j 16 interna-tional units per liter, glutamic oxaloacetic trans-aminase 32 IU per liter, creatine phosphokinase160 IU per liter, glucose 120 mg per dL andalkaline phosphatase 47 IU per liter. The patientrefused admission to the hospital and left after 5hours in the emergency room.

PATIENT 8. A 28-year-old man walked into thehospital complaining of being severely frightenedand of having visual hallucinations and "night-mares." Physical examination revealed no abnor-malities except for diaphoresis and dilated pupilsunresponsive to light. The hemoglobin was 16grams per dL, packed cell volume 48 vols percentand white blood cell count 23,200 per ,tL with 86percent neutrophils, 11 percent lymphocytes and3 percent monocytes. The prothrombin time was10.0 seconds and partial thromboplastin time22.4 seconds. Platelet count was within normallimits. There was a 3 plus reaction for blood inthe urine and a 1 plus reaction for protein. Thepatient remained in the emergency room for sev-eral hours, said he felt better and was discharged.

REFERENCES1. Sunshine I: Handbook of Analytical Toxicology. Cleveland,

Chemical Rubber Co, 1969, pp 394-3952. Mule SJ: Identification of narcotics, barbiturates, ampheta-

mines, tranquilizers and psychomimetics in human urine. J Chro-matogr 39:302-311, 1969

3. Andersen DL: Identification of LSD and other indole alka-loids by ultraviolet degradation products. J Chromatogr 41:491-493, 1969

4. Rubenstein KE, Schneider RS, Ullman EF: "Homogenous"enzyme immunoassay-A new immunochemical technique. BiochemBiophys Res Commun 47:846-851, 1972

5. Fish F, Wilson WD: Excretion of cocaine and its metabolitesin man. J Pharm Pharmacol 21 (suppl):135S-138S, 1969

6. Aghajanian GK, Bing OHL: Persistence of lysergic-aciddiethylamide in the plasma of human subjects. Clin PharmacolTher 5:611-614, 1964

7. Parker KD, Fountan CR, Yee JL, et al: Gas chromatographicdetermination of ethyl alcohol in blood for medicolegal purposes:separation of other volatiles from blood or aqueous solutions.Anal Chem 34:1234-1236, 1962

8. Hoffer A: D-lysergic acid diethylamide (LSD): A review ofits present status. Clin Pharmacol Ther 6:183-255, 1965

9. West LJ, Pierce CM, Thomas WD: Lysergic acid diethyla-mide: Its effects on a male asiatic elephant. Science 138:1100-1103, 1962

10. Louria DB: Lysergic acid diethylamide. N Engl J Med 278:435-438, 1968

11. Brawley P, Duffield JC: The pharmacology of hallucinogens.Pharmacol Rev 24:31-66, 1972

12. Anden NE, Corrodi H, Fuxe K, et al: Evidence for a cen-tral 5-hydroxytryptamine receptor stimulation by lysergic aciddiethylamide. Br J Pharmacol 34:1-7, 1968

13. Boakes RJ, Bradley PB, Briggs I, et al: Antagonism of 5-hydroxytryptamine by LSD 25 in the central nervous system-Apossible neuronal basis for the actions of LSD 25. Br J Pharmacol40:202-218, 1970

14. Martin WR, Sloan JW: Effects of infused tryptamine inman. Psychopharmacologica 18:231-237, 1970

15. Forrer GR, Goldner RD: Experimental physiological studieswith lysergic acid diethylamide (LSD-25). Arch Neurol Psychiat65:581-588, 1951

16. Rinkel M, Hyde RW, Soloman HC, et al: Experimentalpsychiatry II. Clinical and physio-chemical observations in experi-mental psychosis. Am J Psychiat 111:881-895, 1955

17. Friedman SA, Hirsch SE: Extreme hyperthermia after LSDingestion. JAMA 217:1549-1550, 1971

18. Michal F: D-receptor for serotonin on blood platelets. Na-ture 221:1253-1254, 1969

19. Aledort LM, Niemetz J: Dissociation of platelet aggregationfrom clot retraction, potassium loss, and adenosine triphosphataseactivity. Proc Soc Exp Biol Med 128:658-661, 1968

20. Behnke 0: Effects of some chemicals on blood plateletmicrotubules, platelet shape and some platelet functions in vitro.Scand J Haemat 7:123-140, 1970

188 MARCH 1974 * 120 * 3