JAD)A
C LI N ICAL R E PO RTS
Death after chloral hydrate sedation: report of case
J. Theodore Jastak, D D S, P h D
T. Pallasch, D D S, MS
A young healthy female died after taking
chloral hydrate syrup before surgery to
extract third molars. Various aspects of the
use of chloral hydrate are discussed,
including the metabolism, active moiety,
reported side effects, and effects on the heart.
Recommendations are made con cerning
patient supervision, dosage lim itations, and
degree of sedation.
hloral hydrate is widely used as C a convenient,
orally adm inistered sedative in clinical practice,
espe cially in geriatric1,2 or pediatric patients.3'4
A lthough it is considered to be a safe agent,
excessive dosage or unusual circumstances can
result in a substantial risk to the patient. The
follow ing case report is an exam ple of a
healthy young patient dying from a com bination
of circum stances, in c lu d in g u n a n tic ip a te
d overdosage, probable drug interaction w ith
epineph rine, and possible unfam iliarity w ith
the risks of chloral hydrate use.
Report of case
A healthy 22-year-old, 120-lb, 5-ft 4-in
female was adm inistered 2,500 m g of
chloral hydrate syrup. T h e drug was
adm inistered by a dental assistant who,
using a teaspoon, measured the syrup into
a cup. After sw allow ing the contents of
the cup, the patient, w ith a friend, was
perm itted to rem ain in the room u n a t
tended for 10 to 15 m inutes. T he bottle of
chloral hydrate was also left on the coun
tertop during the same period.
About 15 m inutes later, the patient was
escorted to a different room and seated in
a dental chair. After applying a topical
anesthetic, the dentist adm inistered 3.6
m L of mepivacaine during bilateral infe
rior alveolar nerve blocks to provide local
anesthesia before third m olar extractions.
About 35 minutes after the chloral hydrate
was adm inistered, but before the surgical
procedure was begun, the patient asked to go to
the rest room . As a result, she was escorted to
the lavatory by the dental assistant.
A few m inutes later, the assistant heard an
unusual noise from the rest room, forced open
the door, and found the p a tient squatting on the
floor, nodding her head and trying to catch her
breath. Shortly thereafter, the patient was
placed on a rolling chair, moved to another room
where one dentist took her blood pressure (80/40
mm Hg) while sim ultaneously the other dentist
injected 1 mg of epinephrine into the deltoid
muscle. M oments later, both dentists instituted
two-person cardio pulm onary resuscitation
(CPR). Emer gency h elp was called an d w ith
in 10 m in u tes, the re su sc ita tio n effort was
assisted by em ergency personnel. T h e p a tie n
t was given in trav en o u s fluids, sodium
bicarbonate, and two additional intravenous
doses of epinephrine (0.1 mg each). However,
other than some agonal respiratory attem pts, no
pulse or blood pressure could be found and the
patient was transferred to a local hospital while
she was undergoing continuous CPR.
T h e p a tie n t arrived at the h o sp ital about
1 hour and 25 m inutes after the chloral hydrate
was adm inistered and about 40 to 45 m inutes
after the cardiac arrest. At the h o sp ita l, the p a
tie n ts treatm en t in clu d ed five d efib rillatio
n attem pts, five ad d itio n al doses of epi
nephrine, four doses of atropine, two of
intravenous lidocaine, and intravenous fluids.
Unresponsive, she was then trans ferred to a
regional medical center about 60 miles away
where she was pronounced dead 3 hours after
continuous CPR w ith
Table 1 Average trichloroethanol concentration in blood after a single, 825-mg dose of
chloral hydrate.15__________________________________________________________________
N x m axim um concentration T C E (range)
5 9.72 M g/mL (7.6 to 12.2)
out response.
Postm ortem exam ination disclosed no
anatom ic abnorm alities or cause of death. H ow
ever, it was discovered th a t the patients blood
trichloroethanol concen tration was 70.9 jug/mL,
at least five times the norm al therapeutic range
(5 to 15 jug/mL). Serum concentrations of lido
caine used as an an tiarrh y th m ic and
mepivacaine used as a local anesthetic were w
ithin usual therapeutic ranges. Cause of death
was listed as acute chloral hydrate intoxication
(overdose).
Discussion
T he usual recommended adult sedative dose of
chloral hydrate is 500 m g to 1 g taken 30 m
inutes before surgery or sleep. A m axim um
single dose of 2 g is sug gested by the m
anufacturer.5 A lthough the reported dosage in
this case (2.5 g) is mildly excessive, the patients
postm ortem serum concentration of
trichloroethanol (70.9/xg/mL) was substantially
larger than expected from an ingested dose of 2.5
g (Table 1). Clearly, either an error of dos age
was made or during the tim e the patient was
unattended, she medicated herself w ith
additional chloral hydrate from the bottle left on
the counter top.
Chloral hydrate is an alcohol and has little
pharm acologic activity. However, its m ajor
metabolite, trichloroethanol (TCE), appears in
the blood soon after dosing w ith chloral hydrate
and is considered the principal active moeity of
this drug (Fig 1). Peak plasm a concentrations of
TCE occur between 30 and 60 m inutes (Fig 2)
after ingestion of chloral hydrate and w ould
correspond well w ith this p atien ts
x tim e after ingestion (range)
42 m inutes (30 to 60 m inutes)
JADA, Vol. 116, March 1988 345
C LI N I CAL RE PO RTS

showed unexpected, but benign, cardiac

Chloral hydrate Trichloroacetic acid arrhythm ias that resolved spontaneously as the
CL H CL sedation waned. A m ore recent report described
1 i i
three cases of chloral hydrate used after cardiac
CL - C - C - OH x CL-C - C= O
I
I
I
I
I
I surgery in which life -threatening arrhythm ias
CL OH CL OH occurred. Sim ilar to this case, excessive dosage
m ight have had a part in two of the cases.
N j Fig 1 Metabolic fate O verdosage w ith as little as 4 g of chloral
Trichloroethano I (active sedative) of chloral hydrate.
CL H hydrate can cause d e a th .10 People have
1 I ingested up to 30 g of the sedative and survived,
C L - C - C - OH but invariably w ith early an d d efin itiv e d ia g
I I
1 I n o sis follow ed by intense m edical treatm ent.
CL OH R eports of m ajor m orbidity from ch lo ral
\ / Conjugation
J/ hydrate in to x ic a tio n in clu d e acute laryngeal
and excretion
Conjugation and excretion edem a,11 gastric necrosis,12 esophageal
stricture,13 and, in an unusual case involv ing
massive ingestion of a chem ical grade of chloral
hydrate (TCE blood concentra tion of 1700/ig/m
10
L), actually em balm ing
J 8 - Fig 2 Average time
g of the gastrointestinal tract. More specific to this
\
course of plasma tri-

s a- case, however, is the significant incidence of
chloroethanol concen
8 6 cardiac arrhythm ias in peo ple exposed to high
H trations after a single,
825-mg dose of chloral doses of this drug. T able 3 lists com parative
4 - hydrate.15 data from pub lished cases of chloral hydrate
overdose identified from a com puter search of
the literature. (In addition to these cases, other
A
2 -
t i i i i
I papers im plicating cardiac arrhythm ias have
/ t 1
I been published, but w ith insufficient detail to
3 0.511.523 6 // 24
include as data in T able 3.25 27) Wiseman and
Tim e (hr) H em pel28 estimated a 25%

onset of euphoria (loud talking and sing ing) and
sim ultaneously w ith her request to go to the rest
room . Because the patient was alone in the rest
room, the cause of her collapse cannot be
ascertained, but the rapidity of events and the
reported alertness of the patient just before the
col lapse, strongly suggest a sudden cardiac
event rather than a gradually intensifying
respiratory depression ultim ately leading to
cardiac arrest. Alternatively, postural
hypotension secondary to oversedation in an am
bulatory patient m ight also explain
had cardiovascular disease.
U nlike adults, the incidence of unex pected
cardiac com plications in children given sedative
doses of chloral hydrate is unclear. A few articles
in the literature report that cardiac arrhythm ias
occurred in children receiving chloral hydrate.7
9 One of these reported indicated that when
pretreatm ent chloral hydrate sedation was used
for 12 healthy children undergoing elective
electro en cep h alo g rap h y , two
in cid en ce of a rrh y th m ia s in p atien ts
treated for chloral hydrate intoxication. T he data
in Table 3 indicate a majority (13 of 21) of
reported cases had arrhyth mias resistant to
usual drug treatm ent (mostly lidocaine) and
required the use of beta blockers or other
secondary antiar-rhythm ic agents. A lthough the
majority of patients survived even w hen cardiac
arrest occurred, all were correctly diag nosed at
adm ission and treated in inten-

the patients initial condition. Table 2 Adverse reactions from chloral hydrate use in 5,435 adult patients.2
Chloral hydrate is generally thought to have Patients
few side effects when appropriate doses are used. Type of reaction (no.) %
In fact, it is often the pre ferred sedative in both Excessive central nervous system depression
58 1.1
pediatric and geri atric patients.14 A lthough an (daytime disorientation, confusion, ataxia, coma) 12 0.2
old agent,6 recent clinical studies on large num
Excessive central nervous system excitation
bers of hospitalized adults have determ ined an
(agitation, anxiety, hallucination, restlessness) 19 0.3
overall adverse reaction rate of 2.2%2 or 2.3% .1
T able 2 lists the specific types of reactions seen Allergy (rash, fever, eosinophilia, pruritis)
in one population when G astrointestinal disturbance (nausea, vom iting, 15 0.3
diarrhea) 6 0.1
Headache
1 g or less of chloral hydrate was adm inis tered
H epatic decom position 3 0.06
before bedtim e. A lth o u g h m any patients C oagulapathy 2 0.04
were elderly and residing in a chronic disease Cardiorespiratory disturbance (hypotension, 4 0.07
hospital, undesired cardiac events w ithin this dyspnea, arrhythm ia) 119 2.2
population were infre quent, even though a T otal

substantial num ber

346 JADA, Vol. 116, March 1988

 C LI N I CAL RE PO RTS

that the clinician wanted to achieve cen tral

nervous system depression and physi cal control
Table 3 Cardiac arrhythmias induced by chloral hydrate. ap proaching th at seen in patients receiving light
A n tiarrh y th m ic general anesthesia or intravenous sedation, b u t
Dose A rrh y th m ia C ardiac d ru g w ithout the usual controlled environm ent or
Age Sex (g) types arrest resistance O utcom e intensive m onitoring currently considered to be
44 * 12 AF, PVCS X X x 16 a practice standard. O ral sedatives have often
66 F 18 VT, VFib Yes Yes Survived13 been considered safer than other techniques of
48 M 18 PVCS, VT Yes Yes Survived17
central nervous system depression, but may in
2 M 1.5 PVCS No No Survived8
29 F 15 AF No X Survived18
fact be less safe and just as likely to produce side
64 F 10-20 PVCS No No Survived18 effects or conditions usually associated w ith
39 F 30 SVT, PVCS Yes Yes Survived19 general anesthesia and, of course, w ith the same
51 M 25 SVT, VT No No Survived19 risks.32,33 Light or moderate dose regim ens of
21 F 20 VT No No Survived19
oral sedatives providing m ild sedation and
19 F 17.5 PVCS, VFib Yes Yes Survived20
38 F 38 PVCS, VT No Yes Survived21
anxiety control are highly useful and norm ally
33 F 40 PVCS Yes X Died22 represent a very low risk procedure. However,
32 F 20 PVCS, VFib Yes X Survived22 they are not designed for and w ill not provide
17 M 14 PVCS, V T No Yes Survived23 safe physical control or anxiety suppression for
67 F 30 PVCS, VT No Yes Survived23
very frightened patients, for extensive or
29 F 10 PVCS, VT No Yes Survived24
36 F 37.5 CHVT No Yes Survived24 particularly uncom fortable procedures often
57 F 22.5 CHVT No Yes Survived24 encountered in surgery, or for m an agement of
9 F 600 m g f SVT No Yes Survived7 an uncooperative patient.
30 ma F 1400 mg SVT No Yes Survived
10 ma M 500 m g /k g /d SVT No Yes Survived7

*No information provided.

fEvery 6 hr.
AF = atrial fibrillation; Vfib = ventricular fibrillation; PVCS = ventricular premature contractions; SVT = supraventric ular
tachycardia; CHVT = chaotic ventricular tachycardia; and VT = ventricular tachycardia. Summary and recommendations

sive care units. Moreover, several patients were
subjected to more intensive therapy such as hem
odialysis20"22 to reduce drug m etabolite
concentrations in the blood, and most had gastric
lavage to remove unabsorbed chloral hydrate
from the stom ach. In this case, none of these
procedures was perform ed and either accidental
or deliberate overdosage was apparently not
considered.
Chloral hydrate in large doses is be lieved to
shorten the cardiac refractory period and depress
myocardial contractil ity. It also has been
suggested that chloral hydrate, or more
specifically its active metabolites, sensitizes the
myocardium to circulating catecholamines in m
uch the same m anner as chloroform .7,18
Indeed, chloral hydrate and trichloroethanol have
chem ical structures sim ilar to halothane (Fig 3),
an anesthetic know n to sensitize the m
yocardium and the usage of w hich is
recommended w ith strict lim itations on concom
itant adm inistration of adrenergic am ines.29-31
In this regard, it is possible that the initial 1 m g
dosing of epineph rine could have precipitated
the fatal car diac arrest that was then resistant
to norm al therapeutic measures. In support of
this hypothesis, Gerretsen and coau th o rs 22
have suggested th a t in their patients, adm
inistration of adrenergic drugs increased the
incidence of arrhyth mias.
A case of chloral hydrate overdose result ing in
In this case, a safer and more appro p ria te the death of a young healthy female sedated for
em ergency m an ag em en t w ould have been dental care was presented. T he incidence of
not to have given the epineph rine at all, but to cardiac a rrh y th m ia s an d relationship to
have sim ply m aintained a patent airway w ith emergency treatm ent was discussed. T h e
positive pressure, oxygenation if needed, and follow ing recom m enda tions are made: patients
full CPR if an d w hen v ita l sig n s in d ic a te d receiving sedative medications should never be
fu ll cardiac arrest. T he use of large doses of left unattend ed during the induction period;
epinephrine for respiratory distress and only a qualified person should adm inister or
hypotension secondary to sedative medi cations directly supervise the adm inistration of sedative
is not indicated in the absence of drugs; drugs w ith abuse potential should be
electrocardiographic m onitoring or acute carefully accounted for and secured; and the use
bronchospasm caused by anaphylaxis. of high-dosage oral sedative m edications is
discouraged e s p e c ia lly by p e o p le u n tr
Finally, the intent of the sedation used in this a in e d in advanced anesthetic/sedative
case m ust also be considered. The high dose techniques.
adm inistered seems to imply
----------------------- J'AD)A\ -----------------------
CL H
CL ------- C - C ------- OH Chloral hydrate Dr. Jastak is professor and chair, departm ent of hospital
CL OH
dentistry, O regon H ealth Sciences U niver sity, Portland, O R
97201. Dr. Pallasch is associate professor, departm ent of
CL ^ H
pharm acology and p eriodon tics, U niversity of S outhern C
alifo rn ia School of Dentistry, Los Angeles. Address requests
for reprints to Dr. Jastak.
CL- C-C OH
Trichloroethanol
CL H 1. Shapiro, S., and others. C linical effects of hy p notics.
JAMA 209(13):2016-2020, 1969.
CL ^ F
2. M iller, R .R ., and G reenblatt, D .J. C linical effects of
H - -------- C - C --------- P Halothane
chloral hydrate in hospitalized m edical patients. J C lin Pharm
acol 19:669-674, 1979.
BR ^F 3. D uncan, W .K., and others. C hloral hydrate and other
drugs used in sedating young children: a survey of American
Academy of Pedodontics diplom ates. Pediatr D ent 5(4):252-
Fig 3 Com parative chem ical structures of chloral 256, 1983.
hydrate, trichloroethanol, and halothane. 4. W right, G ., and McAulay, D. C urrent prem edi cation
trends in pedodontics. ASDC J D ent C hild
Jastak-Pallasch : DEATH AFTER CHLORAL HYDRATE SEDATION 347
C LI N I CAL RE PO RTS
40:185-187, 1973.
5. Physicians desk reference, O radell, NJ, Medical
Econom ics Co, Inc, 1986, pp 1754-1755.
6. Butler, T . T h e introduction of chloral hydrate into
medical practice. Bull H ist Med 44:168-172, 1970.
7. H irsch, I.A., and Zauder, H .L . C hloral hydrate: a p o
ten tial cause of arrhythm ias. A nesth A nalg 65:691-692, 1986.
8. N ordenberg, A.; Delisle, G.; and Izukawa, T . C ardiac
arrhythm ia in a child due to chloral hydrate ingestion.
Pediatrics 47(1):134-145, 1971.
9. Silver, W., and Stier, M. Cardiac arrhythm ias from
chloral hydrate. Pediatrics 48:332-333, 1971.
10. Gary, N .E., an d Trasznewsky, O. Barbiturates and a p
o tp o u rri of other sedatives, hypnotics and tranquilizers. H
eart L u n g 12(2): 122-126, 1983.
11. Farber, B., and A bram ow, A. Acute laryngeal edem a
due to chloral hydrate. Isr J Med Sci 21:858-859, 1985.
12. Vellar, I.D ., and others. G astric necrosis: a rare com
plication of chloral hydrate poisoning . Br J Surg 59(4):317-
319, 1972.
13. G leich, G .J.; M ongan, E.S.; and Vaules, D.W.
Esophageal stricture follow ing chloral hydrate poi soning.
JAMA 201(4):266-267, 1967.
14. Levine, B., and others. C hloral hydrate: u n u su ally h
ig h concentrations in a fatal overdose. J Anal Toxicol 9(5):232-
233, 1985.
15. Berry, D.J. Determ ination of trichloroethanol at
Temporomandibular joint dysfunction and
orofacial pain caused by parotid gland
malignancy: report of case
Edward G. Grace, DDS, MS
Arthur F. North, DDS, MS
A 41-year-old female with 2 years of
mandibular and maxillary facial pain sought
m ultiple medical evaluations. Symptoms were
similar to those accom panying many benign
temporomandibu lar, salivary gland, and
neurological dis orders. Through manual
palpation, a slight swelling in the salivary
gland was discovered; a malignant carcinoma
was removed by parotidectomy.
F
requently, individuals w ith chronic facial pain
search for care from m any health practitioners.
Dentists as the prim ary care givers form the prelim
inary diagnosis. Both dentists and oral m
axillofacial surgeons need to evaluate for
possible orofacial neoplasms.
T his case report describes the symptoms
348 JADA, Vol. 116, March 1988
therapeutic and overdose levels in blood and urine by electron
capture gas chrom atography. J Gas Chrom a-togr 107:107-114,
1975.
16. M uller, S.A., and Fisch, C. Cardiac arrhythm ia due to
use of chloral hydrate. J Indiana Med Assoc 49:38, 1956.
17. D iG iovanni, A.J. Reversal of chloral hydrate-
associated cardiac arrhythm ia by a beta-adrenergic blocking
agent. Anesthesiology 31(1 ):93-97, 1969.
18. M arshall, A.J. Cardiac arrhythm ias caused by chloral
hydrate. Br M ed J 2:994, 1977.
19. Gustafson, A.; Svensson, S.; and Ugander, L. Cardiac
arrhythm ias in chloral hydrate poisoning. Acta Med Scand
210:227-230, 1977.
20. Vaziri, N .D ., and others. H em odialysis in treatm ent
of acute chloral hydrate poisoning. South Med J 70:377-378,
1977.
21. Stalker, N., and others. Acute massive chloral hydrate
intoxication treated w ith hem odialysis: a clinical pharm
akinetic analysis. J C lin Pharm acol 18:136-142, 1978.
22. Gerretsen, M., and others. C hloral hydrate p o i soning:
its m echanism s and therapy. Vet H u m T o x icol 21
(SuppI):53-56, 1979.
23. Bowyer, K., and Glasser, S. C hloral hydrate
overdose and cardiac arrhythm ias. Chest 77:232-235, 1980.
24. Brown, A.M ., and Cape, J.F. Cardiac arrhyth m ias
after chloral hydrate overdose. Med J Aust 1:28-
leading to the diagnosis and treatm ent of
a m alignant salivary gland tum or. T his
acinous (acinic) cell carcinom a affected the
deep lobe of the parotid gland.
Case report
A 41-year-old white female referred to the
division of oral and m axillofacial surgery at the
Johns H opkins H ospital received evaluation of
right facial pain. Tw o years earlier, the patients
pain had usually occurred w ith dull headaches.
T he pain often involved the right eye and ear,
and was partially relieved by aspirin. The most
recent pain pattern was described as being sharp
during m astication, w ith a persistent dull ache
in the region of the right side of the mandible. T
he patient described an interm ittent
toothachelike pain involving teeth in either the
right posterior part of the m andible or right
29, 1980.
25. King, K., and England, J.F . C hloral hydrate overdose.
Med J Aust 2(6):260, 1983.
26. Baselt, L.C .; W right, J.A.; and Cravey, R .H . T
herapeutic and toxic concentrations of more than 100
toxicologically significant drugs in blood, plasm a or serum: a
tabulation. C lin Chem 21(1 ):44-62, 1975.
27. Bryatt, C., and Volans, G. Sedative and hyp notic
drugs. Br Med J 289:1214-1217, 1984.
28. W isem an, H .M ., and H em pel, G . C ardiac arrhythm
ias due to chloral hydrate poisoning . Br Med J 2:960, 1978.
29. Jastak, J .T ., and Yagiela, J.A. Vasoconstrictors and
local anesthesia: a review and rationale for use. JADA
107(4):623-629, 1983.
30. Jo h n so n , R .R ., an d others. A com parative
interaction of epinephrine w ith enflurane, isoflurane and
halothane in man. Anesth A nalg 55:709-712, 1976.
31. Buhrow, J.A., and Bastron, R.D. A com parative study
of vasoconstrictors and determ ination of their safe dose under
halothane anesthesia. J Oral Surg 39:934-937, 1981.
32. Jdisch, G.F.; Anderson, S.; an d Bell, W.E. C hloral
hydrate sedation as a substitute for exam ina tion under
anesthesia in pediatric ophthalm ology. Am J O phthalm ol
89(4):560-563, 1980.
33. Alpert, C.C., and Salazar, F.G . C hloral hydrate
sedation in children . Letter. Am J O p h th alm o l 90(6):877-
878, 1980.
m axilla. A long history of p opping and
clicking, particularly in the rig h t tem po rom
andibular joint, w ithout an open or closed lock,
bruxism , or clenching habits was reported.
Various physicians and dentists had treated the
patient. Treatm ent in c lu d ed an x io ly tic
agents, occlusal sp lin ts, ex tractio n s, an d en d
o d o n tic therapy.
A nonsmoker who used alcohol only rarely,
the patient had no allergies, and was taking 1 g
of levothyroxine sodium daily for a hypothyroid
condition. Pre vious surgeries included a
tonsillectomy at age 16 and breast biopsy w ith a
benign diagnosis. There were no other medical
illnesses. Family medical history included m
aternal gastrointestinal carcinom a w ith spread
to the liver.
T he patient was subsequently referred to an
oral and m axillofacial surgeon for further
consultation regarding continued