To Xile c Case Studies

7/28/2019 To Xile c Case Studies

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CHRISTINE DIANNE C. PEPITO (Xanthine Derivative)

Theophylline Toxicity: A Case Report of the Survival of anUndiagnosed Patient who Presented to the EmergencyDepartment

ABSTRACT: Theophylline toxicity is a life- threateningtoxidrome that can present to an emergency department.To ascertain an immediate provisional diagnosis intoxicology at the emergency department is verychallenging, especially when the patient presents withaltered mental status, because the clinical features of

several toxidromes overlap. We report a case of survivalof undiagnosed theophylline toxicity that requiredintubation for two days in the intensive care unit. This wasthe first case to have been reported from our department.Accurate diagnosis of a toxidrome by gaining adequatehistory and conducting a thorough physical examinationand early serum toxicology screening, coupled with goodknowledge of toxicology, will lead to better patientoutcomes.

CASE REPORTA 22 year old man was brought to the Emergency

Department (ED) of UniversitiSains Malaysia Hospital(HUSM) by family members 10 hours after the suspectedingestion 30 tablets of chlorpheniramine. He developedintermittent nausea and non- projectile vomiting

(containing food particles) with abdominal pain 2 hourspost- ingestion, and the symptoms persisted until hepresented to the ED. On arrival, he appeared drowsy, butwas not in respiratory distress. His pulse was persistentlytachycardicto more than 120 beats/ minute with a regularrhythm, and he was hypotensive, with a blood pressure of90/ 64 mmHg. His axillary temperature was 37.0C withmoist skin. His pupils were 3 mm bilaterally, equal, andreactive to light. Physical examinations of other systemswere unremarkable. His electrocardiogram showed sinustachycardia, and his capillary blood sugar was 6.7 mmol/L. In the ED, he complained of epigastric pain and urinaryretention. Intravenous metoclopramide (10 mg) wasprescribed to relieve vomiting along with intravenousranitidine (50 mg), followed by activated charcoal. The

patient was still hypotensive despite adequate fluidresuscitation. To restore normal blood pressure, thepatient was started on an infusion of noradrenaline, whichtargets the peripheral alpha- 1 receptor. After 2 hours inthe ED, the patient underwent two generalised tonic-clonic seizures.

Each episode lasted approximately 10 minutesand was aborted with intravenous diazepam. He was givenintravenous phenytoin and was later electively intubatedfor airway protection and cerebral resuscitation. Initialblood gases showed metabolic alkalosis, and he washypokalemic.

The patient was admitted to the Intensive CareUnit (ICU) for monitoring and supportive care. While in theICU, he developed a supraventricular tachycardia (SVT)and synchronised cardioversion (50 J) was delivered,

which successfully reverted him back to sinus rhythm. Thepatient self- extubated on day two of his hospitalisation.His blood pressure was normotensive on inotropic support,but the pulse rate remained tachycardic. Further historyelicited from the patient after he regained consciousnessrevealed that he took 30 tablets of Neulin SR 250 mg. Histheophylline level was assessed immediately, and wasfound to be 40.4 ug/ ml at 72 hours post- ingestion.Repeated blood gases persistently showed mild metabolicacidosis, and he also had increased blood urea andcreatinine. His creatinine phospokinase (CPK) level was>10, 000 IU/ L, but urine myoglobin was negative.Intravenous fluid was increased to 150 ml/ kg/ d, and anintravenous furosemide infusion was started. He was

referred to a nephrologist due to the development ofacute renal failure, and due to the toxic level oftheophylline he was referred for hemoperfusion therapy toenhance theophylline elimination. However, he wastreated conservatively. His theophylline level eventuallydecreased to 20.54 ug/ ml and 2.834 ug/ ml at hospitalday 5 and day 6, respectively. His CPK level decreased to7471 IU/ L, and three repeated urine tests for myoglobinwere negative. His blood pressure and heart rate laternormalised, and he was transferred out to the HighDependency Unit (HDU) at hospital day 7. The patient was

discharged well from the hospital after 2 weeks ofhospitalisation without neurological deficit and withnormalised renal function.FATIMA JAY B. PARADERO (Hallucinogenic Agent)

CASE REPORT

A 20 year old female, who was in police custody, tolda police officer that she felt strange. She then admitted tohaving concealed drugs enclosed in plastic bags in her vaginaWhile a female police officer was helping her to retrieve thedrugs, the patient had a self- limited grand mal seizure. Abroken bag with a crystalline- like substance was found in hervagina.

A second seizure occurred en- route to theemergency department and she presented unresponsive andapneic, requiring endotracheal intubation.

Physical exam revealed:

Temperature: 99.2F

HR: 141 bpm

BP: 144/ 31 mmHg

O2 saturation: 100% with bag valve mask ventilation

Neurological exam- Was significant for decerebrate posturing- Vagina was irrigated with normal saline and there

was no evidence of foreign bodyLaboratory Exam

(-) PT

Glucose: 241 mg/ dl

Creatinine: 1.3 mg/ dl

Na: 143 mEq/ L

K: 3.4 mEq/ L

CO2: 17 mmol/ L

Normal liver enzymes

(-) serum acetaminophen and salicylate concentration

WBC: 15.8 K/ mm3

Haemoglobin: 14.1 mg/ dl and a urine EMIT screen for drugsabuse (+) for amphetamines only

Computerized tomography of the brain was (N)

ECG: shows sinus tachycardia with a ventricular rate of 151bpm

Arterial blood gas: revealed a ph of 7.24 and a base deficit of11 mmol/ L

The patient was given 50 mEq of intravenous sodiumbicarbonate and was transferred to an intensive caretoxicology referral center.

2 hours later, upon arrival to the ICU her vital signs are asfollows:

HR: 132 bpm

BP: 135/ 79 mmHg


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Core temperature: 98F

The patient was ventilated at a rate of 12 breaths/min and O2 saturation was 99% on 50% inspired O2

Neurological Exam

- Was significant for agitation, intermittent myoclonicjerking of all 4 extremities, clonus and hyperreflexia

Vaginal Exam

- Revealed engorged labia and mild erythema of thevaginal wall without any remaining foreign body

GC and Mass Spectrometry of the Urine

- Confirmed the presence of methamphetamine

Quantitative serum concentration- 3100 ng/ ml and 110 ng/ml

REGENT MARIE A. TAN (Herbal Remedies)

CASE OF LIVER DAMAGE IN PATIENT TAKINGHERBAL SUPPLEMENTS

This case is the second fatality to have occurredin the UK. It was reported in a letter to the British MedicalJournal. A 32 year old man was admitted to hospital withfulminate liver failure, otherwise known as massivehepatic necrosis. Within a week of presentation he was

deeply jaundiced and went into coma. Livertransplantation was attempted but did not succeed insaving the patient's life.

Tests were unable to identify any viral,immunological or metabolic cause of liver failure. Fourweeks before presentation the patient had beguntreatment with Chinese herbs for lipomas. Thepractitioner's notes reveal that the patient was born inIndia and had a history of jaundice as a child. Apparentlyhe had also had jaundice in his early twenties. He hadbeen prescribed ten packets of herbs and he had takenone packet of herbs a day as instructed. Throughout theseten days he had felt ill and had diarrhea but he hadpersisted with taking the herbs. After three weeks he wasstill unwell and began to become jaundiced. At this pointhe went to his doctor and was hospitalized.

The following is the herbal prescription as takenfrom the practitioners notes, with the herbs given by theirChinese names.

Pinyinname

Pharmaceutical name Botanical nameDosage

Bai XianPi

Cortex DictamniDasycarpi Radicis

Dictamnusdasycarpus

9 g

ShanZha

Fructus CrataegiCrataeguspinnatifida or C.cuneata

9 g

Zhi Ke Fructus Citri Aurantii Citrus aurantium 4. 5 g

TianHua Fen

Radix TrichosanthisKirilowii

Trichosantheskirilowii

9 g

Chen PiPericarpium CitriReticulatae

Citrus reticulata 3 g

Chi ShaoYao

Radix PaeoniaeRubrae

Paeonia veitchii or P.lactiflora

6 g

DangGui Wei

Radix AngelicaeSinensis

Angelica sinensis 9 g

FangFeng

Radix LedebouriellaeDivaricatae

Ledebourielladivaricata

9 g

Bai ZhiRadix AngelicaeDahuricae

Angelica dahurica 6 g

Fu LingSclerotium PoriaeCocos

Poria cocos 12 g

Bai ZhuRhizoma AtractylodisMacrocephalae

Atractylodesmacrocephala

9 g

Gan Cao Radix GlycyrrhizaeUralensis

Glycyrrhiza uralensis 6 g

DISCUSSION:

One of the tragic features of this case is that hadthis patient stopped the herbs as soon as the diarrheabegan, he would probably still be alive. His death couldalmost certainly have been prevented if he had beengiven written and verbal instructions to stop taking theherbs and contact the practitioner if he should developany symptoms like those of a cold or flu, or any digestivedisturbance such as nausea or diarrhea.

Bai Xian Pi (Cortex Dictamni Dasycarpi Radicis)has been suggested that this herb may be the cause ofthe hepatitis. Since this herb is mostly used to treat skin

disease, this would explain why these cases of liverdamage have been confined to patients being treated forskin disease. However, there are no reports in theliterature of Bai Xian Pi being directly hepatotoxic, and thisincludes a recently published Chinese languagepharmacopoeia which gives details of animal research andclinical studies on this herb34. So if Bai Xian Pi is involved,the mechanism would appear most likely to be a rareallergic hypersensitivity and not direct toxicity.

. Certainly, it has been suggested that severalherbs can be involved in immunoallergic reactions35, andpatients with atopic conditions such as eczema or with ahistory of liver disease might be particularly vulnerable tosuch reactions. In conclusion, it appears almost certainthat the hepatotoxic effect which occurred in this case wasof an immunoallergic type and was not due to a herbwhich is directly hepatotoxic. This has two majorimplications: firstly, that the toxic effect is probably notdose-related, and secondly that these sorts of herbalprescriptions are only potentially toxic to certainindividuals who have an allergy-like sensitivity to them,and do not do any harm at all to the vast majority ofpeople. The problem is to devise strategies to protectthose individuals who do have this immunologicalsensitivity.

it is clear that the incidence of adverse events isquite low, probably affecting one person in tens ofthousands. Most individuals definitely appear to toleratethe herbs without apparent harm, and the clinical trial

results support this conclusion. The problem is that whenthe adverse reaction does occur it can clearly be life-threatening. No-one fully understands the mechanisms ofsuch idiosyncratic reactions, which are also known tooccur with some drugs. It is generally suspected that therecan be a genetic susceptibility which makes someindividuals vulnerable.

It is noteworthy that both of the fatalities involvedpeople of Indian origin. This may indicate a geneticsusceptibility, or it may be that both these individualsalready had compromised liver function, perhaps as aresult of infectious hepatitis earlier in life. In any case, it isclear that people with poor liver function will beparticularly at risk.


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In the light of the above, the RCHM has taken the viewthat whatever the precise mechanisms and whether or nota single herb is the cause, the first priority is to protectfuture patients. In the fatality in particular case mentionedabove,it could almost certainly have been prevented bygood practice, and the RCHM has emphasized this byissuing the following updated guidelines36:

A detailed case history is essential to determine

whether there is any history of jaundice or hepatitis.Where there is such a history, patients must be

closely monitored and this must include liverfunction tests.

Although hypersensitivity reactions are not directly

dose-dependent, continuing caution with dosage isadvised for the time being.

Patients should be carefully monitored, and in

particular practitioners should be alert to any earlysigns of liver damage37.

All patients should be given written guidelines

warning them to stop taking their herbal medicineand immediately contact their practitioner if theyexperience symptoms such as nausea, vomiting,diarrhea, flu-like symptoms, and hypochondriactenderness.

It is important to stress to practitioners, most of whom

have not experienced any problems with their ownpatients being adversely affected, that this does not meanthat there is not a problem. Since it is probable that onlyone person in every few thousand is vulnerable to liverdamage from the herbs, this would mean that one wouldhave to treat five or ten thousand people before onewould expect (statistically) to have one patient become illwith liver damage.It has been suggested by someagencies that all patients being treated with Chineseherbs should receive routine blood tests for liver damage.

CHASTINE DUNGOG (Amphetamin/-like Agents)

Case Report:

A 19 year-old competitive swimmer was pulled from

the pool after a near drowning episode and was found

to be unresponsive and hyperthermic with a

temperature of 108. In the field, she received CPR and

was intubated for altered mental status and respiratory

failure. Patient subsequently developed DIC, profuse

diarrhea, rhabdomyolysis, transaminitis, and acute

oliguric renal failure. Prior to this acute episode, this

patient did remember reporting a headache, having

palpitations, and feeling warm immediately before her

routine swimming practice. She had a past medical

history of ADHD on Adderall, with a dose increase that

same day. She reported taking the medication asprescribed and had no problems with addiction or illicit

drug use in the past per patient and family report.

She was admitted to the Medical Intensive Care Unit

for supportive care including: cooling, volume

resuscitation, multiple transfusions of cryoprecipitate,

fresh frozen plasma, platelets, and red blood cells,

emergent hemodialysis, pressor support, ventilator

support, and broad spectrum antibiotics. The

differential was initially very broad including but not

limited to metabolic abnormalities (fatty acid oxidation

disorders, electron transport chain disorders, glycogen

storage disorders, phosphoglycerate kinase

deficiency), RMSF, sepsis, meningitis, acute HIV,

hepatitis, connective tissue disease, toxin exposure,

amphetamine toxicity, cardiac arrhythmia, heat stroke,

malignant hyperthermia, neuroleptic malignant

syndrome. All of these conditions were thoroughly

evaluated.

Over time, she improved significantly and is currently

back to routine exercise with normal renal function andno measurable deficits. She has remained healthy

during all of her follow up visits.

Discussion: After many laboratory tests and studies,

the primary team and numerous consultants concluded

that the aforementioned event was most likely

secondary to amphetamine toxicity. The patient's urine

amphetamine level was 4390 ng/ml (normal < 50

ng/ml), with an appropriate serum level given her

Adderall dose. She was found to be a slow metabolizer

of this medication, heterozygous for CYP2D6-4

polymorphism, which is associated with an

intermediate metabolizer phenotype. Although we

were uncertain if this could have led to toxic levels ofthe medicine, her symptoms appeared most consistent

with a reaction to amphetamines. Our review of the

literature found only one reported case of

amphetamine toxicity associated with DIC and

hyperthermia with one documented case of Adderall

toxicity in dogs causing hyperthermia and red blood

cell dyscrasia. This case report is the first we are aware

of in the US. This case raised a challenging clinical

scenario given the broad differential and the numerous

life threatening medical conditions that arose so

acutely in a previously healthy individual. Additionally,

concern existed for potential complications with return

to exercise and possible future surgeries requiring

anesthesia. She was advised to not take amphetamine

containing medications, including most ADHD

medications and decongestants.

SITI NADJMAH HADJI TAHA (NSAIDs)

NSAID-induced acute liver failure:A Case Report

Case:

A 39-year old man was admitted to the Department ofInternal Medicine complaining of weakness, nausea,vomiting and epigastric pain which had accrued overseveral days. The patient had been takingDoxycyclinum and Amoxycyclinum for a few days dueto upper respiratory tract infection. Moreover, heconfirmed that he had taken NSAID at high doses(IBUPROFEN 200 mg up to 30 pills a day) for over amonth due to a recurrent toothache.On admission the patient was sweating and lookingpale. A physical examination revealed tachycardia (180beats per minute), normal blood pressure (120/100


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mmHg) and right upper quadrant tenderness onabdominal palpation.

Laboratory tests:Biochemical markers revealed very high levels of total:Bilirubin 3.23 mg/dl (normal 0.3- 1.2mg/dl)Transaminases [ALT 2023.8 IU/l (normal < 40 IU/l)AST 2145.3 IU/l (normal < 40 IU/l)]GGTP 442.8 IU/l (normal < 40 IU/l)Glucose 143.1 mg/dl (normal 60-100 mg/dl)D- dimer 4512.08 (normal < 500)INR 2.148 (normal 0.86-1.30)CRP 22.7 mg/l (normal 0.008- 3.1 mg/l) and there wereno changes in morphology except from slightleukocytosisWBC 11.09 K/ul (normal 4-10 K/uL)Abdominal ultrasonography revealed hepatomegalymarkers of HBV and HCV were negative.Echocardiography revealed dilated cardiomyopathywith EF 20%.An ECG test showed atrial fibrillation (approx. 130 perminute). Since the patients condition dramaticallydeteriorated during the period of hospitalization withdyspnea, cyanosis and a loss of consciousness, withblood gases revealing respiratory insufficiency, the

patient was intubated and ventilated mechanically.

Over the next 36 hours, markers of liver dysfunctionincreased:Levels of ALT- 5176.4 IU/I and AST - 9567 IU/ITotal bilirubin 5.41INR-2.765PT-31.239 sec (normal 12-16 sec) &renal insufficiencywas also observed.

Medication Therapy:Since the intensive treatment including:Cordarone (Amiodarone)Nitracor (Nitroglicerine)Augmentin(Amoxicillinum Acidum clavulanicum)

Furosemide (Furosemide)Nexium (Esomeprazole)Midanium (Midazolam)Phentanyl, Dopamine, Natrium Bicarbonicum, Salinesolution, Atropine, AdrenalineLevonor (Norepinephrine bitartate)Hepa-Merz (Ornithine)Lactulose, Metronidazole & Fresh Frozen Plasma (FFP)

All proved unsuccessful, the patient was transferred tothe Department of Toxicology, to await a livertransplantation

Sedatives and Hypnotics toxicity

Case report #1:

A 5-month-old male, weighing 6 kg, was presented for

a 3rd operation of correction of cleft lip and palate. He

was known to have gastroesophageal reflux, treated

with cisapride and ranitidine. There was no history of

drug allergy, and no pertinent family history. The child

underwent two attempts to repair his cleft lip, at 3 and

4 months of age, both of which failed because of

wound dehiscence caused by extreme postoperative

agitation.

For the 3rd repair, the anesthetic consisted ofpropofol

fentanyl and vecuronium. The plastic surgeon

requested that sedation be continued for 48 h to allow

wound healing to start and avoid previous problems

Therefore, the infant was admitted to the Pediatric

Intensive Care Unit (PICU) where propofol was

continued at a dose of 1 mg.kg-1 h-1 (16.7 ug.kg-1

min-1). 8 hrs postoperatively, he was very agitated and

needed multiple boluses of fentanyl with a gradua

escalation of the propofol infusion rate to 11 mg.kg-1

h-1 (183 ug.kg-1 min-1).

On the 1st postoperative day, the propofol infusion was

increased to 13 mg.kg-1 h-1 (217 ug.kg-1 min-1) to

maintain an adequate level of sedation, in addition to

fentanyl boluses of 33ug.kg-1 total. The laboratory

noted the serum to be grossly lipemic during this time

period.

On the 2nd postoperative day, the propofol infusion

was increased to 15 mg.kg-1 h-1 (250 ug.kg-1 min-1).

During that day, the urine was noted to be green

brown in color and subsequently he developed a

metabolic acidosis: pH 7.21, bicarbonate 18mmol.l-1

The propofol was immediately discontinued. 2 hrs later

he became hypotensive (systolic BP 60 mmHg) and

then oliguric (0.2 ml.kg-1 h-1), for which he received

several fluid boluses. The total dose of propofol given

was 4339 mg over 61.75 h, the mean infusion rate was

11.7mg.kg-1 h-1 (192 ug.kg-1 min-1), and the highest

propofol rate was 15 mg.kg-1 h-1 for 15.5 h.

On the 3rd

postoperative day, the child developed aseries of rapidly changing arrhythmias including: (i

tachycardia,(ii) sinus bradycardia, (iii) 2nd and 3r

degree heart block.Bradycardia was unresponsive to

isoprenaline, dopamine or epinephrine and although

transcutaneous pacing achieved capture, it did not

improve his hemodynamic status. In addition to the

cardiac dysrhythmias, the patient developed

lacticacidosis (day 3), hepatic dysfunction (day 4)

coagulopathy (day 4) and acute renal failure with

hyperkalemia, hyperphosphatemia and rhabdomolysis

(day 6).The child did not receive total parentera

nutrition and was kept nil by mouth because o

episodes of poor perfusion. During the first 3 days ofhis admission, his dextrose intake had been 1.532.7

mg.kg-1 min-1.

Charcoal hemoperfusion was initiated on the 3r

postoperative day when the bradydysrhythmias

started. It was to remove the metabolites of propofo

because propofol itself has a large volume o

distribution and would be poorly cleared from the body

using continuous venovenous hemofiltration. However

water-soluble metabolites and lactic acid are

effectively eliminated with these techniques.The child


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demonstrated marked improvement in heart rate (140

b.min-1 ) and systolic blood pressure (to 90 mmHg)

after 2 h of charcoal hemoperfusion. A second run was

required to normalize his acidbase status and remove

fluid. He subsequently received hemodialysis for 5

days during resolution of his acute renal failure. His

hemodynamic status improved such that he was in

sinus rhythm and all inotropic support was

discontinued by postoperative day 7. He was

extubated on postoperative day 12, with full recoveryof both renal and hepatic function. The child had an

improving neurological status despite a small infarct in

the occipital lobe. He was discharged from hospital 3

weeks after surgery. The presumptive diagnosis in this

case was propofol toxicity.

Discussion

Propofol (2,6-diisopropylphenol) is in many ways an

ideal sedative agent for pediatric intensive care

patients. The benefits of hemodynamic stability, lack of

cumulation or withdrawal make it appropriate for long-

term as well as short-term sedation.

Propofol toxicity might be attributed to impaired fatty

acid oxidation. The disturbance of fatty acid oxidation

could be caused by impaired entry of long chain

acylcarnitine ester into the mitochondria. Propofol has

been shown to impair mitochondrial electron transport

in isolated heart preparations from laboratory animals.

This disturbance of fatty-acid oxidation is consistent

with the clinical picture of propofol toxicity, it may be

precipitated by a combination of prolonged propofol

infusion and a carbohydrate intake insufficient to

suppress fat metabolism.Propofol dose ranges for

maintenance of sedation for radiological proceduresand for anesthesia for major surgery, including lengthy

neurosurgery or orthopedic procedures, vary.In cases

where hemoperfusion was used in cases of propofol

toxicity,our patient responded very well with resolution

of arrhythmias, weaning of inotropes and

disappearance of metabolic acidosis and normalization

of creatinine kinase level.

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