Anaesthesiology perspective on a multidisciplinary approach to optimal perioperative management of a patient with giant peptic ulcer perforation caused by the physiological stress of a thyroid storm necessitating emergent laparotomy
- 1 Department of Anaesthesia, Intensive Care and Pain Medicine, Khoo Teck Puat Hospital, Singapore
- 2 Jurong Health Campus, Anaesthesiology, National University Health System, Singapore
- Correspondence to Dr Dinoo Suran Kirthinanda; dinoo.sn@live.com
Abstract
Thyroid storm is a rare, fatal complication of thyrotoxicosis that necessitates aggressive medical treatment. We present a case of a patient who developed duodenal ulcer perforation as a result of a thyroid storm caused by Graves’ thyrotoxicosis. In addition to life-threatening intra-abdominal sepsis complicated by high anion-gap metabolic acidosis, he was found to have severely deranged thyroid hormone levels and clinical features compatible with thyroid storm based on the Burch-Wartofsky Score. Diagnosis and management of such patients with compromised gastrointestinal (GI) tract present a remarkable clinical challenge to the anaesthetist and the intensivists. Multidisciplinary care with rapid preoperative optimisation, careful intraoperative anaesthetic techniques and postoperative care resulted in excellent outcomes. This case report sheds light on how to tailor general anaesthesia to minimise physiological derangement associated with thyroid storm and re-establish homeostasis in patients presenting for emergent surgery, particularly those with GI dysfunction.
Background
Thyroid storm (TS) is a life-threatening complication of hyperthyroidism often precipitated by trauma, infection, medical illness, or in some cases, surgery. Patients present with a constellation of clinical manifestations including fever, tachycardia, cardiovascular instability and altered consciousness.1 Even with early diagnosis and recent advances in treatment, mortality remains high, in the range of 10%–30%.2 In-hospital mortality of patients with TS appears to be 12-fold compared with patients with thyrotoxicosis without a storm.3
General anaesthesia is known to precipitate TS in patients with thyrotoxicosis. However, the perioperative risk of TS in this category of patients is not quantified. A recent systematic review analysed case reports of unoptimised or partially optimised patients with thyrotoxicosis undergoing general anaesthesia and noted many such patients developed perioperative TS. However, due to the scarcity of evidence and heterogeneity of the existing cohort studies, a meaningful risk stratification remains unfeasible.4
Considering the lethality and the seriousness of the complications, it is advised optimising thyroid status prior to elective or even emergency surgery where possible. Anaesthetising patients with severe thyrotoxicosis or TS carries a high risk of morbidity and mortality. However, in dire circumstances where surgery is lifesaving with little or no time for optimisation, the care teams will face diagnostic and therapeutic challenges of immense proportions.
We report this unique case report of Graves’ thyrotoxicosis complicated by TS presenting with perforated peptic ulcer (PU) due to the physiological stress, requiring emergent laparotomy under general anaesthesia.
Case presentation
A man in his early 50s with no previous medical conditions attended the emergency department for acute onset of right flank and back pain associated with intractable nausea and vomiting and reported a 5-kilogram weight loss, palmar sweating and heat intolerance over the past month. He had been a smoker (40 pack-years) but had no other comorbidities or history of hospitalisation. There was no history of diarrhoea.
On admission, the patient was febrile with a temperature of 38.5°C and tachycardic with a regular heart rate between 140 and 160 beats per minute (bpm). His blood pressure was maintained with systolic pressure ranging between 125 and 165 mm Hg and diastolic pressure ranging between 70 and 95 mm Hg. On examination, generalised abdominal tenderness and guarding were noted. Proptosis, goitre or hand tremors were not elicited.
Investigations
A contrast CT of the abdomen and pelvis showed bowel wall irregularity in the second part of the duodenum with pneumoperitoneum, suggestive of a defect in the lateral wall that may represent possible perforation.
The full blood count showed a marked neutrophil leucocytosis with a total white cell count of 23.48×109/L. Biochemistry showed sodium 138 mmol/L, potassium 3.9 mmol/L, creatinine 57 µmol/L, blood urea nitrogen 5.5 mmol/L and a normal liver function test.
Given the severe tachycardia and compatible history, a thyroid function test was done, which revealed a free tetraiodothyronine level of 90.3 µg/dL and thyroid-stimulating hormone (TSH) of 0.005 mIU/L. The patient’s Burch-Wartofsky Point Scale was 55, indicative of clinical diagnosis of TS.
An ECG showed sinus tachycardia and frequent premature ventricular complexes. The chest radiograph did not show cardiomegaly or pulmonary congestion. He was also suffering from sepsis secondary to peritonitis complicated by lactic acidosis (lactate 5.9 mmol/L). His procalcitonin levels were elevated (14 ng/mL), together with C reactive protein of 206 mg/dL. Arterial blood gas (ABG) showed a pH of 7.302 with bicarbonate 18 mmol/L and a base deficit of 7.8 among other significant blood tests.
Differential diagnosis
Patients presenting with sepsis and features of TS can be challenging to differentiate. Our patient had a history of weight loss, palmar sweating and heat intolerance, which pointed towards a diagnosis of TS. Biochemical confirmation of severely deranged thyroid functions with a supporting Burch-Wartofsky Point Score of 55 (table 1) established the diagnosis of TS. Sepsis presents with similar symptoms and signs owing to the hypermetabolic state confounding the diagnosis. A high index of clinical judgement is crucial in such complex cases.
Calculated Burch-Wartofsky Score at presentation (A) and postoperatively (B)
| Criteria | Points | Patient score |
| Thermoregulatory dysfunction Temperature (°C) |
||
| 37.2–37.7 | 5 | |
| 37.8–38.3 | 10 | |
| 38.4–38.8 | 15 | |
| 38.9–39.4 | 20 | A, B |
| 39.4–39.9 | 25 | |
| ≥40.0 | 30 | |
| Cardiovascular Heart rate (beats/minute) |
||
| 100–109 | 5 | |
| 110–119 | 10 | |
| 120–129 | 15 | |
| 13–139 | 20 | |
| ≥140 | 25 | A, B |
| Atrial fibrillation | ||
| Absent | 5 | A |
| Present | 10 | B |
| Congestive heart failure | ||
| Absent | 0 | A, B |
| Mild | 5 | |
| Moderate | 10 | |
| Severe | 20 | |
| Gastrointestinal–hepatic dysfunction | ||
| Absent | 0 | |
| Moderate (eg, diarrhoea, abdominal pain, nausea/vomiting) | 10 | A, B |
| Severe (eg, jaundice) | 20 | |
| Central nervous system disturbance | ||
| Absent | 0 | A, B |
| Mild (agitation) | 10 | |
| Moderate (delirium, psychosis, etc) | 20 | |
| Severe (seizures, coma, etc) | 30 | |
| Precipitating event | ||
| Absent | 0 | A, B |
| Present | 10 | |
| Total score | ||
| >45 thyroid storm | ||
| 25–45 impending storm | ||
| <25 storm unlikely | ||
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A score of 45 or higher is highly suggestive of a thyroid storm. The patient had a Burch-Wartofsky score of 55 on admission to the emergency department. Postoperatively, his intensive care stay was complicated by fast atrial fibrillation resulting in a postoperative score of 65.
The risk of PU and perforation is known to be increased by factors including Helicobacter pylori infection, old age, history of PUs, gastrointestinal (GI) bleeding, and medications such as aspirin and corticosteroids.5 Our patient did not display these predisposing factors other than a history of smoking. However, considering the temporal pattern of symptoms, it is likely that the patient was suffering from severe thyrotoxicosis, and the resulting severe physiological stress led to the perforated PU. This was supported by elevated thyroid receptor antibodies of 5.7 U/L (reference range <1.8 U/L), which implies that the patient was suffering from Graves’ thyrotoxicosis.
Treatment
Preoperative management
The presence of a gastric perforation required immediate corrective surgery to establish sepsis source control. In order to provide timely preoperative optimisation prior to surgery, we used a multidisciplinary approach involving our colleagues from general surgery, emergency medicine, critical care and endocrinology.
In the presence of PU perforation, administration of oral medications was contraindicated. Alternative rectal and intravenous routes can be used for sympathetic blockade, control of thyroid hormone (TH) synthesis and peripheral conversion. Intravenous esmolol infusion of 50–200 µg/kg/min and intravenous hydrocortisone 100 mg were administered. Hydrocortisone was continued at 100 mg every 6 hours perioperatively. Lugol’s iodine had to be omitted as oral administration of medications was out of the question.
Early administration of propylthiouracil (PTU) is recommended in the presence of TS as it inhibits the production of new THs and prevents the peripheral conversion of tetraiodothyronine (T4) to triiodothyronine (T3), the active form of thyroxine.6 However, duration of 24–36 hours is necessary for a significant therapeutic effect. In cases of the dysfunctional gut, the rectal PTU should be considered. However, in the presence of intra-abdominal sepsis, surgical treatment should not be delayed contingent on the availability of rectal PTU.
Our care teams discussed that treatment options with PTU or Lugol’s iodine would take a few days to weeks in order to have a therapeutic effect on thyroid control, which, in this pressing context of a perforated PU needing immediate operative repair, was not an option. Thus, emergency exploratory laparotomy with omental patch repair was pursued without delay after shared decision-making involving our multidisciplinary team, and the patient was counselled regarding the high perioperative risk.
Intraoperative and postoperative management
The patient was reviewed at the operating theatre reception by the anaesthesia team. Intravenous esomeprazole 8 mg/hour and intravenous esmolol 50–100 µg/kg/min infusions were ongoing. His vital signs remained status quo, although with a small heart rate reduction to below 120/min.
In addition to the standard American Society of Anesthesiologists-recommended intraoperative monitoring, intra-arterial blood pressure, central venous pressure, 5-lead ECG, depth of anaesthesia, core body temperature and neuromuscular blockade were monitored. The emergency cart was on standby with defibrillator pads attached to the patient. An ample supply of resuscitation drugs, including digoxin, inotropes and beta-blockers, was assembled for potential use.
Rapid sequence induction of general anaesthesia was carried out uneventfully with intravenous propofol, lidocaine, suxamethonium and a target-controlled infusion of remifentanil. General anaesthesia was maintained with inhalational sevoflurane and oxygen, intravenous remifentanil infusion and intravenous atracurium infusion. Intravenous esmolol infusion was titrated between 50 and 100 µg/kg/min throughout the surgery for heart rate control. The blood pressure was supported by intravenous phenylephrine infusion with a maximum dose of 1200 µg/hour. Reflex bradycardia observed with phenylephrine was in favour of the clinical situation. Intravenous magnesium sulfate 10 mmol was also administered over 30 min after induction. Heart rate ranged between 90 and 120 bpm during the surgery.
Four-quadrant peritoneal contamination due to a perforated PU was discovered upon entering the peritoneum, which was repaired with an omental patch. Biopsies were taken and the peritoneal washout was done. Surgery was completed uneventfully with minimal blood loss. Aggressive fluid resuscitation, electrolyte optimisation and empirical antibiotics made up the foundation of supportive measures. He was extubated upon completion of surgery and transferred to the surgical intensive care unit for further management.
Insertion of a nasojejunal tube was discussed with the surgical team. Surgical team was of the opinion that the patient could be resumed on clear oral fluids and medication postoperatively by the following day as the likelihood of postoperative ileus was low. As such, the patient’s oral antithyroid medications were commenced within 8 hours of surgery with sips of water.
At the conclusion of surgery, the decision was made to extubate the patient in view of haemodynamic stability and improvement of acidosis on ABG. The neuromuscular blockade was reversed with intravenous neostigmine 2.5 mg titrated slowly without an anti-muscarinic agent to avoid exacerbating TS. There was a transient drop in heart rate (lowest of 60 bpm) after administration of neostigmine. Heart rate remained around 100 bpm throughout the emergence and extubation process. Extubation was uneventful, and the patient was transferred to the surgical intensive care unit for further management. A multimodal analgesia programme, including a patient-controlled analgesia fentanyl, was started for postoperative pain relief. The patient had a transient fast atrial fibrillation postoperatively with a heart rate of 160 bpm. He was normotensive. This was treated with beta-blockers successfully to achieve rate control. Amiodarone was avoided due to the risk of worsening TS. His transthoracic echocardiogram did not show features of cardiac dysfunction.
Outcome and follow-up
There was an ongoing endocrinology review throughout the recovery period. With the surgical clearance, oral Lugol’s iodine 10 drops every 8 hours was administered for the first 7 days postoperatively commencing on the first postoperative day (POD 1). Intravenous hydrocortisone 100 mg every 6 hours was weaned down and stopped on POD 3. Oral PTU 200 mg every 6 hours was started on POD 1, and oral carbimazole 30 mg every morning was commenced on POD 8. The patient remained stable throughout the postoperative recovery period and was discharged from the intensive care unit to the general ward on POD 2.
Intravenous esmolol infusion was weaned off on POD 1, which was replaced by oral propranolol 20 mg three times a day. There was a significant improvement in the patient’s thyroid functions over the next few days. A diagnosis of Graves’ thyrotoxicosis was made given elevated thyroid receptor antibody levels, and the aetiology of the PU was attributed to physiological stress from severe thyrotoxicosis. The patient recovered uneventfully and was discharged home on POD 10 with general surgery and endocrinology follow-up appointments. He had recovered well from both surgery and the thyroid crisis as of the 30-day follow-up. A multidisciplinary collaboration involving the anaesthesiologist, surgeon, intensivist and endocrinologist with a timely intervention was key to good outcome.
Discussion
General anaesthesia is known to precipitate TS in patients with uncontrolled or partially optimised hyperthyroidism. Patients undergoing surgery in the presence of a TS are rare, and there are reports of mortality due to the severe physiological derangements complicating the TS.7
Wartofsky Point Score is widely accepted to be the diagnostic tool for TS. It consists of thermoregulatory dysfunction, cardiovascular, GI manifestations and the presence of a precipitating cause.8 The Japanese Thyroid Association (JTA) proposed new diagnostic criteria for TS in 2016. The criteria required the presence of thyrotoxicosis as a prerequisite condition, and the TS could be diagnosed based on specific combinations of symptoms attributed to multiple organ systems, similar to those listed in the Burch-Wartofsky Point Score. JTA score (table 2) emphasises higher weightage on central nervous system manifestations as opposed to the Burch-Wartofsky Point Scale. Due to the serious nature of the condition, 2016 JTA guidelines and the Japan Endocrine Society (JES) recommended using both diagnostic tools to increase diagnostic accuracy.9 10 In the presence of dual pathologies like sepsis, which could mimic hypermetabolic symptoms of TS, establishing a definite diagnosis could be challenging. Even more so when both conditions are severe and life-threatening. A pragmatic clinical diagnostic approach is warranted in view of the atypical presentations.
Japan Thyroid Association (JTA) diagnostic criteria of thyroid storm (TS)
| Prerequisite for diagnosis | ||
| Presence of thyrotoxicosis: elevated levels of free triiodothyronine (FT3) or free tetraiodothyronine (FT4) | ||
| Symptoms | ||
| 1. Central nervous system (CNS) manifestations: restlessness, delirium, altered mental state/psychosis, somnolence/lethargy, coma (≥1 on the Japan Coma Scale or ≤14 on the Glasgow Coma Scale) | ||
| 2. Fever: ≥38°C | ||
| 3. Tachycardia: ≥130 beats/min or heart rate ≥130 in atrial fibrillation | ||
| 4. Congestive heart failure (CHF): pulmonary oedema, moist rales over more than half of the lung field, cardiogenic shock, or class IV by the New York Heart Association or ≥class III in the Killip classification | ||
| 5. Gastrointestinal (GI)/hepatic manifestations: nausea, vomiting, diarrhoea or a total bilirubin level ≥3.0 mg/dL | ||
| Diagnosis | ||
| Grade of TS | Combinations of features | Requirements for diagnosis |
| TS1 | First combination | Thyrotoxicosis and at least one CNS manifestation and fever, tachycardia, CHF or GI/ hepatic manifestations |
| TS1 | Alternate combination | Thyrotoxicosis and at least three combinations of fever, tachycardia, CHF or GI/ hepatic manifestations |
| TS2 | First combination | Thyrotoxicosis and a combination of two of the following: fever, tachycardia, CHF or GI/hepatic manifestations |
| TS2 | Alternate combination | Patients who met the diagnosis of TS1 except that serum FT3 or FT4 level is not available |
| Exclusion and provisions | ||
| JTA diagnostic criteria recommends exerting clinician judgement as the clinical features are not specific to TS and may represent other pathologies coexisting or otherwise.9 10 | ||
| TS1, ‘definite’ TS; TS2, ‘suspected’ TS | ||
In-hospital mortality appears to be higher in patients with TS compared with the ones without TS (3.5% vs 0.2%). Frequent cardiovascular complications appear to be arrhythmias (96.8%), heart failure (14.2%) and ischaemic events (3.9%).11
Initial resuscitation takes priority in the management, and antithyroid drugs (ATDs) should be considered when the diagnosis of TS is likely. The evidence is, however, weak concerning the ATDs, supplementary drugs and their doses. Although the available clinical evidence for existing TS therapies is not strong, a sound understanding of the pathophysiology should guide the approach to patient management. ATDs therefore remain the mainstay of management of TS. The main action of ATDs is to reduce the synthesis of new THs via direct inhibition of thyroid peroxidases. Methimazole (MMI), carbimazole and PTU are suitable drugs. MMI is available in the intravenous form, although it was not available in our hospital formulary.
Large doses of PTU have been shown to inhibit type I deiodinase resulting in a desirable decrease of peripheral deiodination of T4 to T3 although the clinical advantage of this is uncertain. JES Taskforce, which analysed the nationwide surveys of treatment and management of TS, found no difference in disease severity and mortality in patients who received MMI compared with the patients managed with PTU.12
Beta-blockers are often the only adjuvant required to diminish the sympathetic effects of TS. Non-selective beta-blockers such as propranolol are better suited. They reduce heart rate, blood pressure, myocardial oxygen consumption and contractility. Beta-blockers also inhibit the peripheral deiodination of T4. However, there are reports of circulatory failure and cardiorespiratory arrest after the administration of propranolol or non-selective beta-blockers in patients with congestive cardiac failure or thyroid cardiomyopathy. Hence, it should be used with extreme caution.13 14 Our patient, in particular, was in sepsis. Vasodilation could have precipitated refractory shock. Intravenous esmolol infusion was therefore used. Esmolol is a selective, cardio-specific beta-blocker with an easily titratable pharmacological profile.
Lugol’s iodine or potassium iodide is known to reduce TH secretion. To prevent a surge in TH production, iodine solutions are recommended to be administered 1 hour after initiating ATDs. However, in our case, we did not have the luxury of time nor the ability to administer enteral medicines due to bowel perforation.
Iodinated contrast used for the CT scan may have been beneficial, although this is speculation. Wolff-Chaikoff effect postulates that a large amount of ingested or injected iodine acutely and temporarily inhibits TH synthesis regardless of the serum TSH levels.15 This observation, however, should be substantiated with further research.
Absorption of enteral medicines could be unpredictable in patients with severe GI disturbances due to TS alone. Furthermore, the effects of ATDs and adjuvants take hours or even days to achieve optimal control of TH levels.
Glucocorticoids rapidly block both TH synthesis and peripheral conversion of T4 to T3.16 Glucocorticoids also provide the added advantage of alleviating relative adrenal insufficiency associated with TS, particularly in the presence of sepsis. The use and dosing should be weighed against the potential side-effects such as hyperglycaemia, PU disease and immunosuppression.
There is no strong evidence to encourage or discourage general anaesthetic drugs in the presence of TS or severe thyrotoxicosis. Regional anaesthesia, particularly peripheral nerve blocks, could prove more beneficial considering the minimal physiological derangements associated with this mode of anaesthesia.
When general anaesthesia is unavoidable, we recommend taking a multidisciplinary approach for rapid optimisation and patient preparation for surgery. Avoidance of anticholinergics is prudent as it worsens tachycardia, and there are cases of precipitation of TS following the administration of glycopyrrolate.17 Using rocuronium for the neuromuscular blockade and suggamadex for the reversal of paralysis could avoid the need for anticholinergics.
Potent opioids such as remifentanil are favourable in reducing sympathetic drive and lowering the heart rate. Alpha-2 agonists such as dexmedetomidine or clonidine could also help reduce central sympathetic drive. These drugs have not been extensively studied in the presence of TS. Hence, they should be used with extreme caution, tailoring to individual clinical scenarios as it is unfeasible to predict the precipitation of a TS. Invasive monitoring and central venous access are advocated. The patient should be closely monitored for complications both intraoperatively and postoperatively.
Therapeutic plasma exchange (TPE) should be considered in patients where conventional therapy fails to re-establish normal homeostasis. TPE is believed to exert its effects in the form of the removal of THs, catecholamines and inflammatory mediators.18 Being an invasive procedure with potential complications, TPE is reserved for patients refractory to medical therapy with life-threatening manifestations.
Learning points
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Thyroid storm (TS) with concurrent peptic ulcer perforation is a rare life-threatening amalgamation that requires early diagnosis and prompt treatment.
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In a perioperative setting with dual pathologies, such as coexisting sepsis, the diagnosis of TS could be onerous. To establish an accurate diagnosis and institute appropriate management, a high level of clinical suspicion is required.
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Conventional medical treatment of TS is likely to be ineffective in the presence of gastrointestinal dysfunction. Lifesaving surgical intervention should not be delayed contingent on the availability or the effectiveness of antithyroid drugs to ensure intra-abdominal sepsis is contained.
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Patients should be managed under a specialised multidisciplinary team, and the treatment needs to be tailored to the clinical situation by using anaesthetic techniques and supplementary drugs to counter the widespread sympathetic activation and restore haemodynamic stability.
Ethics statements
Patient consent for publication
Footnotes
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Contributors We would like to state that all persons who are listed as authors below certify that they have participated sufficiently in the submitted work to take public responsibility for the content. SW conceived the idea of the case report and participated in the design, data collection, analysis, drafting of the manuscript, revision of the manuscript and approval of the final manuscript. DSK participated in the design, analysis, drafting of the manuscript, revision of the manuscript and approval of the final manuscript. CC participated in data collection, analysis, drafting of the manuscript, revision of the manuscript and approval of the final manuscript.
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Funding The authors have not declared a specific grant for this research from any funding agency in the public, commercial or not-for-profit sectors.
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Case reports provide a valuable learning resource for the scientific community and can indicate areas of interest for future research. They should not be used in isolation to guide treatment choices or public health policy.
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Competing interests None declared.
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Provenance and peer review Not commissioned; externally peer reviewed.
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References
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