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Case Report

Refractory Hypotension Following Elective Total Hip Replacement Surgery in a Patient Treated With Herbal Medicine: A Case Report

Goh, Hui Fen Jacqueline MMed; Zhang, Mingming MD; Chee, Huei Leng MMed; Chan, Xin Hui Diana MMed

Author Information
A & A Practice: April 2020 - Volume 14 - Issue 6 - p e01172
doi: 10.1213/XAA.0000000000001172
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Abstract

Postoperative hypotension is a potentially life-threatening complication with many possible underlying causes, including hemorrhage, myocardial ischemia, adrenal insufficiency, sepsis, and anaphylaxis.1 Appropriate management consists of simultaneous resuscitation and systematic clinical reasoning to identify the underlying cause and administer timely treatment. We describe a case of refractory postoperative hypotension due to adrenal insufficiency in a patient treated with steroid-adulterated herbal medicine. Written consent was obtained from the patient for the publication of this case report.

CASE DESCRIPTION

A 62-year-old man with a history of chronic kidney disease (baseline serum creatinine, 120 µmol/L; estimated glomerular filtration rate, 56.6 mL·minute−1·1.73 m2), iron deficiency anemia (preoperative hemoglobin, 12.8 g/dL), and penicillin allergy underwent an elective total hip replacement for avascular necrosis of the hip. Surgery was completed under a subarachnoid block with an estimated blood loss of 600 mL. He was hemodynamically stable intraoperatively, and the effects of the subarachnoid block had begun to subside by the time he reached the recovery room. He was monitored in the surgical ward postoperatively with hourly vital signs monitoring.

Eight hours later, he developed profound hypotension with a systolic blood pressure of 60 mm Hg. On examination, he was alert with no complaints of chest discomfort or breathlessness. Heart and lung examinations yielded normal findings, and his calves were supple. The surgical dressing was dry, and surgical drain output was minimal. Laboratory investigations and the electrocardiogram were not suggestive of hemorrhage, sepsis, or myocardial ischemia. Vancomycin had been given intraoperatively for antibiotic prophylaxis in view of his penicillin allergy, otherwise no new medications had been started postoperatively.

The patient was transiently responsive to fluid resuscitation but subsequently became hypotensive again, despite receiving 2.5 L of intravenous fluids and 1 unit of packed red blood cells (pretransfusion hemoglobin level was 7.9 g/dL, which may have been contributed by hemodilution from fluid resuscitation). He was admitted to the intensive care unit because of hemodynamic instability, requiring high doses of epinephrine, norepinephrine, and vasopressin. A computed tomography (CT) pulmonary angiogram did not demonstrate pulmonary embolism, and bedside echocardiogram showed normal heart function. Blood cultures were performed, and antibiotics were escalated to intravenous vancomycin and aztreonam to cover for possible sepsis. Continuous renal replacement therapy was commenced to correct the severe acidosis from organ hypoperfusion (arterial blood gas [ABG] pH 7.052; base excess, −16.5 mmol/L; serum bicarbonate, 8.3 mmol/L). A random cortisol level was found to be 360 nmol/L, which was considered inappropriately low 24 hours after a moderately invasive surgery such as a hip replacement, where a more pronounced systemic stress response and cortisol surge was expected.2 A provisional diagnosis of adrenal insufficiency was made, and the patient was given intravenous hydrocortisone (100 mg, 8 hourly for 5 days). His condition stabilized rapidly and vasopressor support was weaned, after which he was extubated. His kidney function also recovered quickly, and the hydrocortisone supplementation was tapered off over 4 days.

Further history from the patient’s family revealed that he had been taking various herbal medications for his hip pain, some of which were obtained overseas. The medications were tested in the Pharmaceutical Laboratory of the Health Sciences Authority (Singapore), the local governmental regulatory agency, and one of the medications sourced from Thailand was found to contain prednisolone, cyproheptadine, and piroxicam. The patient had taken the medication regularly for 1.5 years and stopped 1 day before his surgery. He had not informed his doctors about these herbal therapies preoperatively.

An adrenocorticotropic hormone (ACTH) stimulation test was performed on postoperative day 12, 3 days after the last hydrocortisone dose. Serum cortisol was measured immediately before and at 30 and 60 minutes after intravenous injection of 250 µg of cosyntropin, a synthetic derivative of ACTH, which stimulates maximal adrenocortical secretion for the test duration.3 Cortisol levels measured during the challenge test were 490, 600, and 597 nmol/L, respectively, which was equivocal. However, a morning cortisol level measured on postoperative day 8 was found to be only 200 nmol/L despite intravenous hydrocortisone supplementation. This was suggestive of inappropriately low cortisol secretion, as cortisol levels are usually highest in the morning (ranging from 275 to 555 nmol/L), and hydrocortisone supplementation increases cortisol levels.3 Furthermore, a paired baseline morning plasma ACTH level taken with the ACTH stimulation test on postoperative day 12 was found to be low at 3.1 ng/mL, which was in keeping with secondary or tertiary adrenal insufficiency. These findings strongly supported the diagnosis of adrenal insufficiency, likely secondary to long-term exogenous steroid intake from the adulterated herbal medication.

DISCUSSION

Although the patient’s medication was labeled as containing extracts from pure Thai herbs, prednisolone, piroxicam, and cyproheptadine had been added. The pills were effective in alleviating his joint pain, as may be expected from the anti-inflammatory and analgesic effects of prednisolone and piroxicam. The patient had stopped the medication 1 day before surgery and developed refractory hypotension 2 days later. Extensive workup eventually attributed the complication to steroid-induced adrenal insufficiency.

Herbal medicine is a well-accepted form of complementary medical therapy for a wide range of ailments, including cancer, chronic pain, respiratory, and dermatological conditions. Traditional Chinese medicine (TCM) is among the most well-known and is popular among the Chinese population, but there are other forms of herbal medicine, such as Indian Ayurveda, Indonesian/Malay Jamu, Thai traditional medicine, Korean traditional medicine, and Japanese traditional medicine, which are highly sought after among other populations.4–7

Patients often seek herbal medicine for its touted “natural and safe” profile. Unfortunately, adulteration involving the addition of undeclared drugs is a cause for concern. Common adulterants include steroids, nonsteroidal anti-inflammatory drugs (NSAIDs), oral hypoglycemic agents, antihistamines, and phosphodiesterase inhibitors.8–11 The incentive behind adulteration of herbal medication is easily understood, as they are frequently marketed as effective treatment for chronic pain, skin problems, and respiratory problems.

Steroids are among the most common adulterants and are often added with NSAIDs for joint pain or general weakness.10,11 They are effective relievers of inflammatory pain but are known for causing severe side effects, such as Cushing syndrome, adrenal insufficiency, peptic ulcer disease, and immunosuppression when used for protracted periods. In Singapore, the Health Sciences Authority detects about 10 cases of complementary health products adulterated with corticosteroids each year, through reports submitted by health care professionals.12

Aside from steroidal adulteration, some herbs have intrinsic steroidal activity. For instance, the steroidogenesis effect of Cordyceps sinensis mycelium has been demonstrated in mice,13Herba epimedii water extract has been found to elevate estrogen levels in postmenopausal women,14 while deer musk extracts have been used as natural androgens to enhance performance in elite athletes.15 Nevertheless, a recent study on TCM concluded that very few TCM herbs have clinically relevant steroidal activity.11 On the other hand, adulterated herbal products are a recurring cause of steroid-related adverse events.10,11 We were not able to trace the herbal components of our patient’s medication as it was a home recipe from a Thai doctor who was no longer contactable, but it is possible that the herbs had intrinsic steroidal activity in addition to the prednisolone.

A high index of suspicion for acquired adrenal insufficiency is necessary when searching for causes of hypotension. This is particularly vital in cases of perioperative hypotension, as patients may stop taking their herbal medications preoperatively without informing their physicians. Of course, a better way is prevention. Detailed history taking during the preoperative assessment may aid in the identification of adulterated herbal products. Questions should be asked regarding the use of complementary health products and herbal medications, including their indications, therapeutic effects, and side effects. Suspicion should arise if the patient reports an immediate analgesic effect after consuming the products. On retrospective questioning, our patient reported experiencing good pain relief after taking the Thai medication. In addition, he experienced increased appetite, weight gain, and gastric discomfort, which may have been side effects of prednisolone, piroxicam, and cyproheptadine. High-dose steroid therapy is also a common cause of avascular necrosis; the surgical diagnosis was an invaluable clue that the patient may have been exposed to steroids, but it was unfortunately overlooked. This highlights the importance of considering the patient’s history in its entirety. If steroidal adulteration had been suspected before surgery, the herbal medication could have been optimally tapered, steroids supplemented perioperatively, and the life-threatening complication may have been avoided.

CONCLUSIONS

Herbal medicine is a widely popular form of complementary medical therapy, often marketed as natural and without side effects. In seeking such therapies, patients may unknowingly consume adulterated products. The present case is a timely reminder for physicians to not overlook the use of herbal medicine and to suspect potential medication adulteration within the proper context. Patients taking herbal therapies may not readily volunteer this information; thus, doctors should routinely ask their patients about the use of herbal medicine and complementary health products as part of a comprehensive medical assessment. This information may be crucial for the management of complications and will aid in the identification and reporting of adverse events arising from the use of adulterated health products. Such vigilance is especially important in this age of global medicine, where patients come from all over the world with different cultural and health beliefs.

DISCLOSURES

Name: Hui Fen Jacqueline Goh, MMed.

Contribution: This author helped conceive, draft, and review the manuscript.

Name: Mingming Zhang, MD.

Contribution: This author helped conceive, draft, and review the manuscript.

Name: Huei Leng Chee, MMed.

Contribution: This author helped conceive, draft, and review the manuscript.

Name: Xin Hui Diana Chan, MMed.

Contribution: This author helped conceive, draft, and review the manuscript.

This manuscript was handled by: BobbieJean Sweitzer, MD, FACP.

GLOSSARY

ABG = = arterial blood gas

ACTH = = adrenocorticotropic hormone

CT = = computed tomography

NSAID = = nonsteroidal anti-inflammatory drug

TCM = = traditional Chinese medicine

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