Water Intoxication Caused by an Overdose of Powdered Herbal Medicine: A Case Report

Abstract

ABSTRACT

Large doses of powdered herbal medicines can cause water intoxication due to excessive water intake. Clinicians should consider this risk alongside the medicine's side effects for timely diagnosis and management.

Introduction

Acute drug intoxication is a common occurrence in the emergency department, with many symptoms similar to those of overdose. When the substance causing the poisoning is unknown, a diagnosis can be made using a toxidrome, which estimates the causative agent based on vital signs, physical findings, symptoms, blood tests, and electrocardiogram (ECG) features. However, it should be kept in mind that patients may also be affected by factors other than the ingested drugs themselves. This case report discusses the importance of considering the possibility of water intoxication without being confused by the situation at hand.

Case History

A 43-year-old man was found collapsed in his home. His speech was incoherent, and he was confused. He was transported to the hospital via ambulance. His medical history included depression. An inspection of his home revealed 50 empty packages of the Japanese herbal medicine “Keishikaryukotsuboreito” (Figure 1), which was purchased over the Internet and had arrived on the day of admission. This was the first time he had purchased herbal medicines, and he did not take the drug for suicidal purposes but wanted to lift his mood.

[IMAGE OMITTED. SEE PDF]

Although the patient had been depressed for several years while attending a psychiatrist, he had discontinued psychiatric consultations and medication approximately 3 years prior to admission. Therefore, at the time of ER admission, the patient was not taking any antipsychotic or mood-stabilizing medications. He also had no history of taking herbal medicines.

After the ambulance's on-scene arrival, the patient started making a fuss and refused to go to the hospital; therefore, he was taken to the hospital approximately 2 h after symptom onset. Upon hospital arrival, the patient's Glasgow Coma Scale scores were E3, V2, and M5. His temperature was 37.0°C, heart rate was 98 bpm, respiratory rate was 24 breaths/min, blood pressure was 150/80 mmHg, peripheral blood oxygen saturation was 99%, and pupillary response was 3.5+/3.5+. He was of medium build, with a height, weight, and BMI of 179 cm, 66 kg, and 22.8 kg/m², respectively. His physical findings were within normal limits, except for significant bruising on his back. Behaviorally, he was delirious and uncooperative.

Differential Diagnosis, Investigations, and Treatment

We performed gastrointestinal decontamination to maximally aspirate the patient's gastric content. After the procedure, he developed sudden seizures despite having no prior seizure history. A single dose of intravenous diazepam (5 mg) was administered, effectively terminating the seizures. No recurrent seizures were observed, and prophylactic anti-epileptic drugs were not deemed necessary. Computed tomography of the patient's head confirmed the absence of any intracranial lesions. We performed magnetic resonance imaging and electroencephalography of the patient's head, the findings of which were unremarkable. The ECG showed no arrhythmias or other obvious abnormal findings. A urine drug screening test was negative for methamphetamines, opiates, addictive stimulants, cannabis, cyclizine, benzodiazepines, barbiturates, methadone, tricyclic antidepressants, and zolpidem. Furthermore, comprehensive toxicology screening was conducted using blood, urine, and gastric samples, but no specific toxins, including any components of the herbal medicine “Keishikaryukotsuboreito,” were detected.

We assessed the patient's serum sodium (114 mmol/L), chloride (104 mmol/L), urine specific gravity (1.001), urine osmolality (34 mOsm/kg), and urine sodium (6 mEq/L) levels—all of which were low. Other laboratory tests revealed a serum creatinine phosphokinase level of 3090 U/L, potassium level of 4.8 mmol/L, adjusted calcium level of 8.6 mmol/L, and alcohol concentration of 0 g/L.

Syndrome of inappropriate antidiuretic hormone secretion was ruled out, given his hypotonic urine. Additionally, he had no history of oral medications that stimulate antidiuretic hormone secretion. Based on the patient's presentation and test results, we concluded that he had experienced water intoxication. There was no episode of him drinking a lot of water up until the onset of this case. The basic treatment for water intoxication in psychogenic polydipsia is water restriction [1]. In psychogenic polydipsia, serum sodium levels often improve quickly with water restrictions, whereas serum sodium levels unexpectedly rise, which is often difficult to correct [2]. In this case, his serum sodium level improved promptly with water restrictions, so correction with 3% saline was not performed.

The patient's fluid intake was restricted to 1000 mL per day. Serum sodium levels were re-evaluated every 6 h, and fluid intake was adjusted accordingly to ensure gradual correction without rapid fluctuations. With this treatment, his serum sodium level slowly increased from 119 to 139 mg/L (Figure 2). The patient was initially treated for hyponatremia, and on the third day of admission, his creatinine phosphokinase levels rose to a maximum of 151,405 U/L. At that point, his serum sodium levels were normal, and renal function was preserved. To prevent acute kidney injury, active intravenous replacement with isotonic saline was started at 150 mL/h and adjusted based on urine output and renal function. The patient's renal function was maintained throughout the course of treatment, and his creatinine phosphokinase levels decreased gradually without complications. The patient was hospitalized for 13 days, during which his condition gradually improved. We present the changes in vital signs and blood test results from the time of admission to hospitalization in Table 1.

[IMAGE OMITTED. SEE PDF]

TABLE 1 Trends of vital signs and blood test results.

Day		0						1	2	3	4	5	6	7	8
	Minutes (after coming to a hospital)	0	60	90	120	180	240
Consciousness	JCS	20	30R	spasm	100	20	20	20	3	2	2	1	0	0	0
GCS	E3V2M5	E4V2M4	E1V1M5	E3V2M4	E3V2M4	E3V2M4	E4V4M5	E4V4M6	E4V4M6	E4V5M6	E4V5M6
Vital	Body temperature (°C)	38.2						37.4	36.9	37.3	37	36.9	36.7	37.1	36.8
Blood pressure (mmHg)	150/80			139/81	103/99	110/101	120/109	155/82	147/85	144/93	170/80	134/90	142/71	116/89
Respiratory rate (/min)	23	20	40	19	20	20	23	20	19	17	12	18	18	19
Heart rate (/min)	93	106	95	85	94	110	119	90	99	80	70	80	80	78
SpO2	100	100	92	99	99	100
	Pupil (R/L)	3.5/3.5
	Pupil reflex	=+/+	'=+/+		'=+/+	'=+/+	'=+/+	'=+/+	'=+/+	'=+/+	'=+/+	'=+/+	'=+/+	'=+/+	'=+/+
In/out (mL)	In						500	500	3600	6000	4900	4600	5170	3970	2820
Out						3500	5695	3580	3580	5100	3000	4250	5850	750
Balance						−3000	−5195	20	2420	−200	1600	920	−1880	2070
Blood test	WBC (/μL)	20,700						13,200	8800	10,400	8900	7300	8700	7200	9900
CK (U/L)	3069						15,299	116,518	151,405	89,870	85,384	18,081	2916	145
AST (U/L)	65						189	1012	1343	996	1102	436	117	21
ALT (U/L)	40						56	226	318	306	336	265	154	24
Cre (mg/dL)	0.53						0.66	0.71	0.65	0.66	0.64	0.66	0.7	0.7
BUN (mg/dL)	4						4	5	5	4	5	9	9	9
Na (mmol/L)	119	127		134	138	139	139	142	141	142	140	141	143	136
K (mmol/L)	3.6						3.4	3.7	4.8	4	3.9	3.5	3.7	3.9
Cl (mmol/L)	81						103	106	104	105	104	106	106	98
Mg (mg/dL)										1.9	1.8	2	2.1
Ca (mg/dL)	8.6									8.8	8.9	8.7	8.5
P (mg/dL)	1.6									2.6	3.1	2.7	3.3

Upon discharge, he was referred to the psychiatric department for ongoing management. He is currently attending follow-up appointments once a month and continues to take antipsychotic medications as part of his treatment regimen. The patient is stable and continues to be closely monitored by the psychiatric team. His overall prognosis is positive, and he has not experienced any recurrence of the acute symptoms associated with water intoxication.

Discussion

“Keishikaryukotsuboreito” is traditionally used to treat insomnia, irritability, and anxiety caused by fatigue and nervousness. It comprises seven components mixed at the following ratio: keishi 4.0 (Cinnamon Twig), syakuyaku 4.0 (Peony Root), taisou 4.0 (Jujube), borei 3.0 (Oyster shell), ryuukotsu 3.0 (Longgu), kanzo 2.0 (Licorice), and syoukyou 1.5 (Ginger Extract). Unfortunately, we could not find any further details regarding its contents.

When assessing patients who have ingested herbal medicines, each component's side effects should be considered [3]. Several side effects of herbal medicines have been reported in the literature [4], including pseudohyperaldosteronism [5] and drug-induced liver dysfunction [6] associated with licorice ingestion. There have also been reports of ocular side effects [7]. However, to the best of our knowledge, no consciousness disorders or restlessness have yet been reported as adverse reactions to “Keishikaryukotsuboreito” ingestion. Hyponatremia caused by water intoxication was also observed in our case; however, there have been no published reports of hyponatremic side effects caused by the components of Chinese herbal medicines.

Our patient had consumed 33.3 g of licorice, which exceeds the acceptable daily intake. The occurrence of licorice side effects is associated with its dose [8], intake duration [9], and susceptibility [10]. Licorice, a key ingredient in the herbal medicine “Keishikaryukotsuboreito,” contains glycyrrhizin, which can have significant effects on the body's electrolyte balance. Glycyrrhizin has been known to cause sodium retention and potassium excretion, leading to hyperaldosteronism-like effects, which can contribute to the development of hyponatremia, especially when coupled with excessive water intake. This mechanism may have played a role in the patient's hyponatremia in this case, although the contribution of water intoxication from the large volume of water ingested remains a central factor. While the patient did not show classic signs of licorice-induced pseudoaldosteronism, it is important to note that even a short-term or acute overdose of licorice can cause significant disturbances in electrolyte homeostasis.

A large quantity of water is generally required to ingest powdered medicines, and this amount scales significantly as the drug dose is increased. Each packet ingested by our patient contained a single dose of “Keishikaryukotsuboreito” (2.5 g). The patient ingested 50 packets of this herbal medicine for a total dosage of 125 g (Figure 1), with each packet requiring approximately 100 mL of water for ingestion. Therefore, it is estimated that the patient consumed at least 5000 mL (5 L) of water in total. Although the exact volume of water consumed was not recorded during the incident, this estimation highlights the substantial amount of water ingested, which may have contributed to the development of water intoxication. Thus, our case illustrates that when large amounts of powdered oral medicines (including herbal medicines) are ingested, it is necessary to consider not only the drug's side effects but also the possibility of water intoxication.

In the past, cases of hyponatremia caused by water intoxication have been reported after patients consumed large quantities of herbal beverages to improve physical health and mental well-being. Certain therapies also use herbs to maintain good physical health, stabilize mental illnesses, and as a way of “cleansing and purifying” the body. It is believed that consuming large quantities of water with these herbs can flush harmful waste from the body. There have been cases reported in the literature of hyponatremia caused by water intoxication that resulted from the use of such therapies in conjunction with excessive water intake [11–13].

When treating hyponatremia caused by water intoxication, it is important to be cautious regarding the occurrence of rhabdomyolysis (RML). RML can cause kidney dysfunction by releasing muscle components such as myoglobin and creatine kinase into the bloodstream. RML related to water intoxication can occur through the following two mechanisms: (1) impaired sodium-calcium exchange increases intracellular calcium, activating enzymes that damage cells [14], or (2) reduced extracellular osmotic pressure causes muscle cell swelling and membrane fragility [15]. Rapid sodium correction can exacerbate these effects. A study reported that 55% of RML cases occurred during water intoxication treatment, suggesting a link to rapid sodium correction [16]. Since RML treatment requires hydration, which contradicts water intoxication management, careful monitoring and timely intervention are essential.

Overdoses and water intoxication are common in psychiatric patients, with psychogenic polydipsia causing hyponatremia through excessive water intake. However, large doses of herbal or powdered medicine may induce similar symptoms through a different mechanism. In this case, the patient's psychiatric history and dosing errors increased his vulnerability, highlighting the risk of self-medication with herbal remedies. Clinicians should assess the potential for excessive intake of both fluids and herbal medicines in psychiatric patients. Patient education on proper dosage, fluid monitoring, and the risks of licorice-containing products is crucial for prevention.

Conclusion

This case highlights the importance of considering water intoxication in patients who have overdosed. Particularly when high doses of powdered medicines, including herbal medicines, are involved, it is necessary to be aware not only of the side effects of the drugs themselves but also of the large volume of water consumption required when ingesting these drugs. By recognizing this possibility, we can speed up proper diagnosis and management and prevent the potentially fatal complications associated with water intoxication in these patients.

Author Contributions

Yukari Maki: writing – original draft, writing – review and editing. Asuka Tsuchiya: supervision. Yoshihide Nakagawa: supervision. Seiji Morita: supervision.

Acknowledgments

We would like to express our gratitude to the editor for their valuable comments and suggestions, which helped improve the quality of this manuscript.

Ethics Statement

All procedures performed in this study were in accordance with the ethical standards of the Helsinki Declaration.

Consent

Written informed consent was obtained from the patient to publish this report in accordance with the journal's patent consent policy.

Conflicts of Interest

The authors declare no conflicts of interest.

Data Availability Statement

The data that support the findings of this study are available from the corresponding author upon reasonable request.

References

P. Reddy, “Clinical Approach to Euvolemic Hyponatremia,” Cureus 15 (2023): e35574, https://doi.org/10.7759/cureus.35574.

S. Tandukar, R. H. Sterns, and H. Rondon‐Berrios, “Osmotic Demyelination Syndrome Following Correction of Hyponatremia by ≤ 10 mEq/L per Day,” Kidney360 2 (2021): 1415–1423, https://doi.org/10.34067/kid.0004402021.

Y. Shimada, “Adverse Effects of Kampo Medicines,” Internal Medicine 61 (2022): 29–35, https://doi.org/10.2169/internalmedicine.6292‐20.

I. Arai, Y. Harada, H. Koda, K. Tsutani, and Y. Motoo, “Estimated Incidence per Population of Adverse Drug Reactions to Kampo Medicines From the Japanese Adverse Drug Event Report Database (JADER),” Traditional & Kampo Medicine 7 (2020): 3–16, https://doi.org/10.1002/tkm2.1234.

T. Makino, “Exploration for the Real Causative Agents of Licorice‐Induced Pseudoaldosteronism,” Journal of Natural Medicines 75 (2021): 275–283, https://doi.org/10.1007/s11418‐021‐01484‐3.

N. Mantani, T. Kogure, J. Tamura, Y. Shimada, and K. Terasawa, “Challenge Tests and Kampo Medicines: Case Report and Review of the Literature,” American Journal of Chinese Medicine 31 (2003): 643–648, https://doi.org/10.1142/s0192415x03001259.

F. W. Fraunfelder, “Ocular Side Effects From Herbal Medicines and Nutritional Supplements,” American Journal of Ophthalmology 138 (2004): 639–647, https://doi.org/10.1016/j.ajo.2004.04.072.

N. Mantani, R. Yamaguchi, and Y. Sekiguchi, “Development of Pseudo‐Aldosteronism Depends on Amount of Glycyrrhizae Radix in Each Individual,” Traditional & Kampo Medicine 58 (2007): 273–276.

N. Mantani, H. Oka, Y. Sahashi, et al., “Relationship Between Incidence of Pseudoaldosteronism and Daily Dose of Glycyrrhiza: Review of the Literature,” Traditional & Kampo Medicine 66 (2015): 197–202.

Y. Morimoto and C. Nakajima, “Pseudoaldosteronism Include by Licorice Derivatives in Japan,” Journal of Medical and Pharmaceutical Society for Wakan‐Yaku 8, no. 8 (1991): 1–22.

M. Soliman, W. Fuller, N. Usmani, and O. Akanbi, “Acute Severe Hyponatremia as a Serious Health Implication of Herbal Detox Regimens,” Cureus 10 (2018): e3697, https://doi.org/10.7759/cureus.3697.

M. K. Jangid, N. Panchal, and P. N. Reddy, “Hyponatremic Seizure in an Autistic Child Associated With Excessive Water Intake With Herbal Medicine,” Pediatric Oncall 17 (2020): 88–89.

O. T. Toovey, I. R. Edmond, and N. Makris, “Acute Severe Hyponatraemia Secondary to Polydipsia and Associated Herbal Remedy Use,” BMJ Case Reports 2016 (2016): bcr2016216348, https://doi.org/10.1136/bcr‐2016‐216348.

P. C. Singhal, M. Abramovici, and J. Venkatesan, “Rhabdomyolysis in the Hyperosmolal State,” American Journal of Medicine 88 (1990): 9–12, https://doi.org/10.1016/0002‐9343(90)90120‐3.

D. A. Rizzieri, “Rhabdomyolysis After Correction of Hyponatremia due to Psychogenic Polydipsia,” Mayo Clinic Proceedings 70 (1995): 473–476, https://doi.org/10.1016/0002‐9343(90)90120‐3.

M. Kashiura, M. Kobayashi, H. Abe, et al., “Study of the Pathogenesis and Prognosis of Rhabdomyolysis in Water Intoxication Patients,” JJAAM 24 (2013): 767–773, https://doi.org/10.3893/jjaam.24.767.