Journal of Forensic and Legal Medicine 96 (2023) 102530

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Journal of Forensic and Legal Medicine

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Case report

Methamphetamine-induced profound rhabdomyolysis and myoglobin cast

nephropathy: A case report and a literature review
Nantapong Chansaengpetch , Wisarn Worasuwannarak *, Suchin Worawichawong
Department of Pathology, Faculty of Medicine Ramathibodi Hospital, Mahidol University, Bangkok, Thailand

A R T I C L E I N F O A B S T R A C T

Handling Editor: Wilma Duijst
A 46-year-old male with a history of substance abuse was found dead in custody 30 hours post incarceration for a
minor offense. The scene demonstrates the body lying in a prone position in the cell room, locked from the
outside. No signs of violence were found at the scene. External examination revealed no significant injuries,
except for multiple minor contusions and abrasions. The autopsy demonstrated only a moderate degree of
bilateral pulmonary edema. No internal injuries were found, except for fractures in the three lower left ribs.
Dark reddish-brown urine was detected in the urinary bladder. Histological examination revealed a diffuse
tubular injury with intraluminal eosinophilic granular casts. The myoglobin cast demonstrated pale PAS staining
with a granular appearance, Masson Trichrome staining demonstrated fuschinophilic deposits on the casts, and
immunoperoxidase staining for myoglobin was strongly positive in the casts (the images will be displayed). Blood
myoglobin and creatine kinase levels were elevated. These findings revealed profound rhabdomyolysis caused by
several factors. Blood toxicology tests revealed lethal methamphetamine and amphetamine levels. All the
findings were consistent with methamphetamine-induced severe rhabdomyolysis. Therefore, forensic patholo­
gists should carefully search for gross and histological findings and conduct thorough laboratory investigations to
diagnose this condition for complete medicolegal examination.

1. Introduction tachycardia, high blood pressure, vasospasm, and myocardial infarc­

Drug-related death is common globally. According to the United
Nations Office on Drugs and Crime, the estimated number was approx­
imately 585,000 between 2008 and 2012, while in Thailand, 81% of the
causes of drug-related deaths were from methamphetamine
intoxication.1,2
Substance or illicit drug use can lead to sudden death, such as car­
diovascular toxicity from Cocaine, Cannabis, or Marijuana use.3,4
Although Cannabis and Marijuana are well known to be used for rec­
reational purposes or as a long-term medication with a few adverse
events, there have been reports of cardiovascular events and sudden
death.4 Heroin, or the synthetic form of morphine, stimulates the
parasympathetic nervous system and inhibits sympathetic activity in the
central nervous system. Hypotension, bradycardia, and respiratory
depression can lead to death.5
Amphetamine and its derivatives stimulate the autonomic nervous
system and secrete serotonin, dopamine, and norepinephrine, leading to
tion.6 Furthermore, they directly affect myocytes and induce seizures,
repetitive muscular activity, and hyperpyrexia via dopamine receptor
stimulation. All the above mechanisms result in rhabdomyolysis.6
Rhabdomyolysis is characterized by severe skeletal muscle damage
and injury. It causes muscle lysis, increased creatine kinase enzyme
levels, electrolyte imbalance, acute renal failure, and disseminated
intravascular coagulopathy. Common causes are muscular trauma,
muscle enzyme deficiency, electrolyte imbalance, infection, drugs, and
toxins.3 However, the clinical triad of rhabdomyolysis: muscle pain,
weakness, and dark urine, was found in less than 10% of the patients and
usually there were no symptoms in more than 50% of the patients.7
Ecstasy (MDMA), MDA, and MDEA are Amphetamine derivatives8
that also stimulate serotonin, dopamine, and norepinephrine secretion
in the CNS. MDMA acts at the 5-HT synapse and inhibits the reuptake
transporters, leading to increased intra-synaptic concentrations of
transmitters and periods of depletion,9 which leads to overstimulation of
the sympathetic nervous system, hemodynamic instability, agitation,

* Corresponding author. Department of Pathology, Faculty of Medicine Ramathibodi Hospital, Mahidol University, 270 Rama VI Road, Ratchathewi, Bangkok,
10400, Thailand.
E-mail address: Wisarn.wor@mahidol.ac.th (W. Worasuwannarak).

https://doi.org/10.1016/j.jflm.2023.102530
Received 13 June 2022; Received in revised form 14 April 2023; Accepted 22 April 2023
Available online 24 April 2023
1752-928X/© 2023 Elsevier Ltd and Faculty of Forensic and Legal Medicine. All rights reserved.
N. Chansaengpetch et al. Journal of Forensic and Legal Medicine 96 (2023) 102530

and irritability.10 Moreover, it can cause hyperpyrexia owing to 5-HT crime scene investigation team should comprise a prosecutor, a police
and dopamine activation in CNS thermoregulation center.11 Overall, officer, a forensic pathologist, and a district governor. The scene
rhabdomyolysis is a rare condition.12 A study demonstrated that fatal demonstrated that the body was found lying in a prone position in a cell
rhabdomyolysis was found in 52 out of 33194 forensic autopsy cases room locked from the outside, with no evidence of body movement post
(0.15%). Drug-induced rhabdomyolysis is the second leading cause of death. A full meal box was placed inside the cells. No signs of violence or
death from rhabdomyolysis, following blunt force trauma.13 bloodstains were observed.
In this report, the authors present a case of sudden death in custody,
wherein severe rhabdomyolysis was detected with extreme amphet­
2.1. External examination
amine and methamphetamine levels. An interesting finding was the
pathological change in the kidney associated with myoglobin cast ne­
On external examination of the body at the scene, minor contusion
phropathy. We also reviewed the literature and discuss the causes and
wounds were found around the anterior leg area, and multiple shallow
mechanisms of drug abuse-related rhabdomyolysis.
abrasion wounds were found at the forehead, upper and lower back,
both knees, and bony prominence area of both hips. Both hands were
2. Case report
clenched, and no significant lethal injuries were observed during
external examination. The body was cold to touch. Full rigor mortis of all
A Thai male, 46 years old, was found dead in a prison cell (Fig. 1) at a
extremities and fixed livor mortis at the front of the body were observed.
police station in central Bangkok post 30 h in custody due to a minor
The cornea was clear and the eyes were closed. The male’s face was
offense of drug possession and a history of drug abuse. According to the
compatible with age. No jaundice or subconjunctival hemorrhage was
police, the decedent had clinical symptoms of agitation, confusion, and
observed in either eye.
aggressive behavior prior to death. According to Criminal Procedure
From the examination at the autopsy room 13 h after the scene ex­
Code section 150, in Thailand, whenever a death occurs in custody, the
amination, the body weight was 49 kg, and the height was 165 cm. An

Fig. 1. The location of the decedent in custody.

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N. Chansaengpetch et al. Journal of Forensic and Legal Medicine 96 (2023) 102530

early cloudy cornea and mild greenish discoloration in the right lower
area of the abdominal region were observed.

2.2. Autopsy findings

Autopsy demonstrated intercostal muscle hemorrhage in the anterior

left side corresponding to rib fractures on the same side from the 5th to
7th ribs. Chronic pleuritis was observed in the right lung, with moderate
pulmonary edema in all lobes on both sides. A small metallic Garuda-like
amulet was found in the middle part of the esophagus (Fig. 2). The heart
revealed no coronary atherosclerotic changes and no evidence of
macroscopic pathological changes with normal weight. The descending
colon revealed focal hemorrhage. The kidneys demonstrated congestion
(Fig. 3), and no specific pathological changes were observed in other
organs.
Blood was collected from the femoral vein into sodium fluoride and
heparin tubes for toxicological testing. The urine appeared dark
brownish, which was collected using a syringe and stored in a bottle
(Fig. 4).

2.3. Microscopic examination Fig. 3. The cross-section of the kidneys demonstrating congestion.

Samples of the visceral organs: brain, heart, lung, liver, spleen,

pancreas, kidneys, and adrenal glands were fixed in 10% formalin and
embedded in paraffin. Furthermore, microtome-cut sections, 2–3 μm
thick, were collected and stained using the hematoxylin-eosin (H&E)
method. Microscopic examination of the lung tissue revealed moderate
pulmonary edema with pleural thickening, which was consistent with
chronic pleuritis. The heart tissue revealed no myocardial infarction,
and the other organs demonstrated no specific pathological changes.
The kidney tissues were cut at 2-μm thickness and stained for H&E,
PAS, Masson trichrome and Jone’s. The microscopic examination
revealed foci of dilated renal tubules with loss of brush borders and
intratubular sloughed epithelial cells compatible with acute tubular

Fig. 4. Dark-brownish urine was collected from the deceased.

injury (ATI). Intratubular luminal casts composed of eosinophilic round

granules line up in chains or aggregate in clusters. The immunoperox­
idase staining for myoglobin showed strongly positive reactivity in the
casts, consistent with myoglobin cast (Fig. 5).

2.4. Toxicology and chemical testing

Blood ethanol level (GC-HS): not detected (<5.00 mg/dl).

Screening for drugs and drugs of abuse from blood (LC/MS/MS):
Fig. 2. A small metallic Garuda-like amulet found in the upper third of positive for methamphetamine, cotinine, and caffeine. Quantitative
the esophagus. analysis demonstrated amphetamine at 2.806 mg/l and

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N. Chansaengpetch et al. Journal of Forensic and Legal Medicine 96 (2023) 102530

Fig. 5. The histopathology of the myoglobin casts in the kidney. A. Diffuse tubular injury with intraluminal eosinophilic granular casts (H&E x 400). B. The
myoglobin cast depicts pale PAS staining with granular appearance (PAS x 400). C. The Masson trichrome staining demonstrates fuschinophilic deposits on the casts
(Masson trichrome x 400). D. The immunoperoxidase staining for myoglobin is strongly positive in casts (x 400).

methamphetamine at 1.794 mg/l, which were lethal levels.14 vasoconstriction, and induced pulmonary hypertension.6
Screening for drugs and drugs of abuse from urine (LC/MS/MS): Drug and substance abuse can cause rhabdomyolysis via multiple
positive for amphetamine, methamphetamine, cotinine, and caffeine. mechanisms. The mechanism of action of amphetamine and its de­
Serum chemistry: rivatives involves stimulation of the secretion of serotonin (5-hydroxy­
tryptamine), dopamine, and norepinephrine in the CNS. 5-HT and
Serum myoglobin:1268 ng/ml (normal 28–72 ng/ml)
dopamine are substances that act in the CNS associated with the ther­
Serum creatine kinase: >426,700 u/l (normal 30–200 u/l) moregulation of the body; therefore, MDMA substance activates this
pathway, leading to hyperpyrexia, and is also one of the causes of
Serum creatinine 6.88 mg/dl (normal 0.73–1.18 mg/dl) rhabdomyolysis.9 The stimulant effect of amphetamine leads to the
repetition of muscular activity or direct toxicity of skeletal myocytes.
The sympathetic effect causes vasoconstriction, hypoperfusion, volume
depletion, CNS effects, hyperpyrexia, hypokalemia, agitation, and
3. Discussion
extrapyramidal effects. A combination of etiological factors can lead to
muscle dysfunction.15 All of these factors lead to rhabdomyolysis (see
The decedent suddenly died from an unknown cause while in cus­
Fig. 6). Herein, the deceased had a clinical symptom of agitation before
tody for two days after being arrested for drug abuse. He developed
death; therefore, the stimulant effect of amphetamines should be the
delirium before death. External examination of the body revealed no
cause.
significant external injuries or abnormalities. Autopsy revealed no sig­
The clinical presentation of rhabdomyolysis usually begins with
nificant gross pathology, except for dark brownish urine. Therefore, the
weight reduction, loss of muscle integrity, and change in urine color.
authors focused on the chemistry and toxicology evaluation of blood or
Consistently, in our case, red-brown urine was observed. The decedent
urine. Not surprisingly, chemical analysis demonstrated highly elevated
had a history of drug-related charges, which increased the suspicion of
serum myoglobin, serum creatinine, and serum creatine kinase levels in
rhabdomyolysis.
the blood, consistent with profound rhabdomyolysis.
The autopsy and histological examination of this case revealed pul­
Rhabdomyolysis could occur from many causes, including skeletal
monary edema at a moderate level, and this condition is the most
trauma, muscular vessel occlusion, excessive exercise of the muscles,
common pathological finding in cases of death from drug-related abuse.
electrical current, hyperthermia, metabolic, drugs, and toxins such as
The etiology is ambiguous and poorly understood, but studies from
cocaine, ecstasy, amphetamine, and methamphetamine.15
molecular pathology believe it is likely caused by multiple genes and
In the autopsy and examination of sudden death with custody, the
degradation of pulmonary endothelial cells, increasing vascular
author focused on physical abuse injuries, including musculoskeletal
permeability from vascular endothelial cell injury, leading to pulmonary
trauma, which is one of the causes of death and rhabdomyolysis. In this
microcirculation disorder and pulmonary edema.1,16
case, there were no signs of significant physical abuse injuries, muscu­
Ingestion of ethanol with illicit drug use can lead to rhabdomyolysis
loskeletal trauma, or major injuries, except for multiple shallow abra­
with acute and chronic effects. The rapid mechanism involves a change
sions found in external injuries. Thus, death from trauma or torture is
in mental status, deterioration of consciousness, and muscle compres­
less likely.
sion. Chronic effects lead to electrolyte imbalance and increase the
Toxicology analysis demonstrated lethal amphetamine and meth­
chance of rhabdomyolysis.17 The author investigated ethanol levels in
amphetamine levels in the blood, which could be the cause of rhabdo­
this case, but ethanol was not detected. This may be as he did not
myolysis and death. Amphetamines are sympathomimetic drugs that can
consume ethanol prior to the charge, or as the decedent had been in
lead to sudden death due to arrhythmia or dysrhythmic activities (e.g.,
custody around two days before death, his blood ethanol level decreased
prolonged QT), cardiomyopathy, coronary atherosclerosis of the heart,

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N. Chansaengpetch et al.
Fig. 6. Mechanism of amphetamines-induced rhabdomyolysis.
to zero.
The laboratory tests for rhabdomyolysis diagnosis are serum
myoglobin and creatine kinase. Creatine kinase (CK) is typically found in
the striated muscle. If the muscle is damaged or traumatized, it is
released into the bloodstream. The creatine kinase enzyme is more
stable than myoglobin; therefore, it is more reliable in post-mortem
diagnosis.15 It was not much affected by post-mortem change,
although it gradually increased after death.18 Increased levels of en­
zymes with severe electrolyte abnormalities lead to acute renal failure
and sudden death.19 The serum creatine kinase level can reach 70,000
IU/ml10. The average CK level was higher in the methamphetamine user
group than in the non-methamphetamine group.10 There is no definite
cut-off value for rhabdomyolysis diagnosis; however, CK is usually
10-times more than the upper normal limit of approximately 1000 u/l,
and serum myoglobin tends to be used as a predictor of acute kidney
injury condition.20 In addition, the serum creatinine level in this case
reached 6.88 mg/dl indicating acute renal failure.21 This level is reliable
because it is stable for three days after death.22
An increase in urine myoglobin level also indicates massive skeletal
injury. Immunohistochemical staining of kidneys can be used to di­
agnose acute renal failure due to rhabdomyolysis.23
The results of amphetamine and methamphetamine blood levels in
this case were 2.806 mg/l and 1.794 mg/l, respectively, indicating lethal
levels.24 This case study thus concludes that combined use of
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Journal of Forensic and Legal Medicine 96 (2023) 102530
methamphetamine and amphetamine to increase the stimulant effect or
mixed effect25 was the cause of rhabdomyolysis and death.
In addition to amphetamines, some other drugs or toxic substances
can cause rhabdomyolysis. Cocaine and phencyclidine can also cause
this condition by developing EPS and increasing the muscle activity.
Clofibrate and ethanol can also cause rhabdomyolysis via direct
musculoskeletal injury.26
4. Conclusion
Death in custody is a case that a forensic pathologist can encounter.
Several factors may contribute to death, including trauma, torture,
natural diseases, and drug abuse, which should be thoroughly examined.
This case report presents a rare event, wherein death due to profound
rhabdomyolysis was triggered by methamphetamine abuse. Rhabdo­
myolysis is one of the critical mechanisms of death that should be
considered when conducting a post-mortem examination or autopsy,
especially in cases of death in custody. A forensic pathologist should
carefully investigate gross and histological findings and consider labo­
ratory investigations to diagnose this condition for a complete medico­
legal examination.
N. Chansaengpetch et al.
Ethical clearance
This report has been approved by the Ethical Clearance Committee
on Human Rights Related to Research Involving Human Subjects, Fac­
ulty of Medicine, Ramathibodi Hospital, Mahidol University, MURA
2021/801. Written consent of the next of kin was obtained.
Funding
This research did not receive any specific grant from funding
agencies in the public, commercial, or not-for-profit sectors.
CRediT authorship contribution statement
Nantapong Chansaengpetch: Conceptualization, Formal analysis,
Methodology, Investigation, Writing – original draft. Wisarn Wor­
asuwannarak: Conceptualization, Project administration, Supervision,
Writing – review & editing, Manuscript submission. Suchin Wor­
awichawong: Conceptualization, Investigation, Writing – original
draft.
Declaration of competing interest
The authors declared no conflict of interest.
Acknowledgments
We would like to thank our colleagues, including the staff and offi­
cers of the Division of Forensic Medicine, for the support they have given
us.
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