Dr. Vasanthi Vidyasagaran*

Department of Anaesthesiology, Kauvery Hospital, Chennai, Tamilnadu, India

*Correspondence: Vasanthi.vidyasagaran@gmail.com

Dr. Vasanthy Vidyasagaran Muralidharan

PERI-OPERATIVE

Chapter 03

Disulfiram Like Reaction

A 42-year-old man presented to the casualty, with degloving injury to his right forearm. He was a case of drunken driving. He was immediately prepared for surgery to salvage his limb. Initial workup and investigations were sent and the patient was wheeled into the operation theatre. His last oral intake was 120 ml of Whisky 1 hour ago.

He was conscious, oriented, and talking clearly. Clinical evaluation of his cardiorespiratory system was normal. He was very apprehensive and would not agree to a brachial plexus block. Rapid sequence intubation was performed under the cover of a broad-spectrum antibiotic, (Ciprofloxacin/metronidazole combination.) Surgery was allowed to proceed.

The orthopedic and the vascular surgeons managed to salvage the limb in 3 h. At the end of surgery patient was adequately reversed. His recovery was extremely stormy. Tachycardia of 144/min, BP of 180/110 mm Hg. He was restless, and agitated and vomiting in spite of using Ondansetron and ranitidine

The cause of this unpleasant recovery was looked for.

There were no untoward events in the intraoperative period to precipitate such a recovery. Saturation was 98%, he was hydrated and urine output was maintained, respiration was adequate. Adequate analgesia and anxiolytics were administered. Our next suspicion was drug interaction–a Disulfiram like reaction due to the use of Ciprofloxacin/metronidazole in a patient who had consumed alcohol recently. Supportive care was provided for the next 5 h. Adequate intravenous fluids and pain relief was ensured. Stomach was emptied. Patient recovered gradually.

Discussion

Interesting reactions and unexpected scenarios in recovery must be dealt with very careful thought process. A number of drug interactions can be anticipated in patients under the influence of alcohol coming up for emergency surgery. There is enough evidence to suggest that some drugs exhibit Disulfiram like reaction with alcohol, where they inhibit hepatic alcohol dehydrogenase and enhance serum levels of acetaldehyde. (Disulfiram is a drug discovered in the 20th century, used to treat chronic alcoholism by producing acute sensitivity to ethanol.)

This may cause flushing, throbbing headache, dyspnoea, nausea, copious vomiting, diaphoresis, thirst, chest pain, palpitations, hyperventilation, hypotension, anxiety, blurred vision, confusion, and arthropathy. In severe reactions, respiratory depression, CV collapse, arrhythmias, MI, acute heart failure, seizures, unconsciousness, or even death may result.

Drugs implicated include:

  1. Antibiotics (Imidazoles, Sulfonamides, some Cephalosporins, Nitrofurantoin, Chloramphenicol)
  2. Antifungals (Griseofulvin)
  3. Industrial solvents
  4. Mushrooms (Coprinus atramentarius [inky cap], Clitocybe claviceps)
  5. Pesticides. (Carbamates, Monosulfiram [Tetmosol)
  6. Chloral hydrate

Clinical presentations may include neurological toxicity, cardiovascular collapse and associated gastrointestinal toxicity symptoms.

Neurologic toxicity increases with dose and duration of therapy and may include central and peripheral sensory motor neuropathy, diffuse toxic axonopathy, psychosis, limbic system stimulation by Dopamine, and catatonia.

We need to differentiate this from delirium tremens due to alcohol withdrawal or reduction. Symptoms of frank delirium tremens are delirium with clouding of sensation, visual disturbances, shivering, and rise in temperature.

Scope for research

Imidazole derivatives (etomidate, clonidine, dexmedetomidine, ketoconazole) are extensively used in medicine and anaesthesia. Hence, we must exert utmost caution when using these drugs anticipating drug interactions. There is great scope for research in this group of drugs in anaesthesia and analgesia. Metronidazole has long been implicated in disulfiram like reaction with ethanol. However, there is upcoming evidence to suggest that it may not always be the case and it is important to note that not all Imidazoles react.

References

[1]Sertac Guler, et al. Disulfiram-like Reaction with Ornidazole. Am J Em Med. 2015;33:P1330.E7-1330.E8

[2]Samara Soghoian. Disulfiram Toxicity: Background, Pathophysiology, Epidemiology medicine.medscape.com/article/814525-overview Jan 6,

As an Anaesthetist, we need to know drug interactions and/or do the necessary references when an unanticipated reaction occurs.

PERI-OPERATIVE

Fat Embolism During Liposuction

A 35-year-old woman was admitted to undergo liposuction of abdomen and lateral aspect of the thigh. She weighed 140 kg. All her preoperative investigations including chest x-ray were normal. The plan was to perform the surgery under general anaesthesia. Two wide bore (16G) intravenous lines were started and the patient preloaded with 1000 ml of crystalloid.

Airway was secured with 7 size cuffed endotracheal tube after induction with Propofol, Fentanyl, and Vecuronium as muscle relaxant. Urinary bladder was catheterized.

Surgery began with the abdominal site, 45 minutes into the procedure, patient desaturated up to 94%. The tube position was checked and she was manually ventilated with 100% oxygen. Saturation improved in a few minutes and mechanical ventilation was resumed with 50% oxygen.

This happened thrice. During these episodes, there was gradual increase in heart rate from 90 to120/min. The plane of anaesthesia was deepened but the heart rate did not come down. Urine output was maintained at 40 ml/hour. After an hour of surgery, the oxygen saturation dropped to 90% and did not improve even with 100% oxygen.

The reservoir bag was tight. Auscultation revealed crepitations. 80 mg intravenous Furosemide was given. Crepitations persisted. Heart rate was 120/minute and BP was 90/40 mm Hg. The procedure was quickly completed and further surgery was abandoned. Abdominal bandages were applied. Arterial blood gas analysis showed acute hypoxia with paO2 value 56 mm Hg on FiO2 100%. A small dose of vasopressor was used to maintain hemodynamic stability. Patient was not dehydrated as urine output was maintained.

She was shifted to the intensive care unit for elective ventilation and supportive management. At that point, the differential diagnoses were:

  1. Pulmonary oedema due to over hydration
  2. Embolic phenomenon (air/fat/thrombus)

We were trying to identify, analyse, and rule out issues commonly encountered in obese surgical patients such as hypoventilation, anaphylaxis, endobronchial intubation as well as inadequate relaxation and anaesthesia causing bronchospasm. Ventilatory support was continued. After 5 hours of care in the ICU, patient regained consciousness.

Petechial rashes were noticed on her neck, shoulder and axillary region. A diagnosis of fat embolism was made. CTPA (pulmonary angiography) was performed and diagnosis of pulmonary embolism was confirmed. The treatment for the same had already been initiated with elective ventilation. Her oxygen requirement gradually reduced. Fortunately, she responded well to treatment and was extubated after 48 hours. She remained hemodynamically stable.

Discussion

Fat embolism syndrome (FES) is one of the most serious complications of liposuction. Other major complications include sepsis, perforation of abdominal or thoracic viscera, haemorrhage, hypotension, pulmonary embolism, pulmonary oedema, necrotizing fasciitis, and cardiac arrest.

FES is an uncommon life-threatening complication of long bone fractures, typically manifesting 24-72 hours after initial trauma and/or in the intraoperative period. The typical clinical symptoms of FES include acute respiratory failure, global neurological dysfunction, and petechial rash. In patients with isolated respiratory symptoms, the presence of hypoxemia and pulmonary infiltrates are easily confused with other more commonly encountered problems, such as aspiration pneumonia, left ventricular overload with pulmonary oedema, or lung contusion.

In normal course of events, the solution used in the liposuction technique eases process of extraction of subcutaneous tissue with reduced rate of tissue injury. When fat tissue is badly damaged and surpasses the ability of plasma to decompose, large amounts of free fat enter the blood and cause fat embolism syndrome (FES). This is the most significant complication causing mortality in liposuction and is rare.

Statistics also show that the development of pulmonary embolism may be associated with the amount of fat removed during liposuction surgery (>1500 g). Echocardiography to check left ventricular function and Broncho-alveolar lavage to confirm diagnosis of fat embolism may be done.

In the event of deterioration in patient condition, immediate supportive measures must be given and surgery terminated as soon as possible ensuring haemostasis. Warning signs such as raised ventilator pressures, hypoxia and desaturation, hemodynamic instability must not be ignored. Lung compliance must be checked manually with bag and auscultation of chest would give clearer clinical picture.

Patients who are overweight or obese, have risk of developing deep vein thrombosis, which may occur in the immediate postoperative period. Case reports of cerebral events and peripheral limb embolic events have been reported. Doppler study may be necessary to establish the diagnosis. Measures to prevent DVT such as stockings, use of LMWH, must be taken in the perioperative period.

References

[1]Xiaoliang Fu, et al. Fat Embolism as a Rare Complication of Large-volume Liposuction in a Plastic Patient. J Forens Sci Med. 2015;1:1; 68-71

[2]The Evidence for Plastic Surgery. 2008. Edited by Christopher Stone, Pg. 54

[3]Fodor PB. Reflections on lipoplasty: History and personal experience. Aesthet Surg J 2009;29:226-31.

[4]Hughes CE 3rd. Reduction of lipoplasty risks and mortality: An ASAPS survey. Aesthet Surg J 2001;21:120-7

[5]Lehnhardt M, Homann HH, Daigeler A, Hauser J, Palka P, Steinau HU. Major and lethal complications of liposuction: A review of 72 cases in Germany between 1998 and 2002. Plast Reconstr Surg 2008;121:396e-403

[6]Pell AC, Hughes D, Keating J, Christie J, Busuttil A, Sutherland GR. Brief report: Fulminating fat embolism syndrome caused by paradoxical embolism through a patent foramen ovale. N Engl J Med 1993; 329:926-9.

[7]Fourme T, Vieillard-Baron A, Loubií¨res Y, Julie C, Page B, Jardin F. Early fat embolism after liposuction. Anesthesiology 1998;89:782-4.

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