|Year : 2016 | Volume
| Issue : 3 | Page : 455-457
Copper and anesthesia − a surprising connection
Pradnya M Bhalerao, Kalpana V Kelkar, Anand H Pande, Bapu P.G. Kakade
Department of Anaesthesiology and Critical Care, B.J. Medical College and Sassoon General Hospitals, Pune, Maharashtra, India
|Date of Submission||04-Jun-2015|
|Date of Acceptance||31-Mar-2016|
|Date of Web Publication||31-Aug-2016|
Pradnya M Bhalerao
D-15/10-11, Saritanagari-2, Off, Sinhagad Road, Pune 411030, Maharashtra
Source of Support: None, Conflict of Interest: None
A 28-year-old female presented with complaints of fever with chills and dizziness on and off for the last 3 months. On admission, she was investigated and found to have anemia and thrombocytopenia. On examination, the patient was pale and had a palpable huge spleen. Past history revealed a diagnosis of Wilson’s disease 15 years ago. This disease, due to altered copper metabolism, may influence the conduct and outcome of anesthesia secondary to abnormalities in hemopoietic, cardiovascular, connective tissue, immune, and nervous systems. In this study, we present a patient, a diagnosed case of Wilson’s disease, with massive splenomegaly posted for splenectomy under general anesthesia and the concerns involved therein.
Keywords: general anesthesia, splenomegaly, Wilson’s disease
|How to cite this article:|
Bhalerao PM, Kelkar KV, Pande AH, Kakade BP. Copper and anesthesia − a surprising connection. Ain-Shams J Anaesthesiol 2016;9:455-7
|How to cite this URL:|
Bhalerao PM, Kelkar KV, Pande AH, Kakade BP. Copper and anesthesia − a surprising connection. Ain-Shams J Anaesthesiol [serial online] 2016 [cited 2021 Apr 17];9:455-7. Available from: http://www.asja.eg.net/text.asp?2016/9/3/455/189569
| Introduction|| |
Excess copper accumulation due to reduction in the synthesis of the copper transporter protein ceruloplasmin causes failure of excretion of copper into bile and it accumulates in body tissues leading to major hepatic and neurological involvement. This altered copper metabolism may influence the conduct and outcome of anesthesia secondary to abnormalities in hemopoietic, cardiovascular, connective tissue, immune, and nervous systems. Wilson’s disease (WD) is an autosomal recessive disorder with an estimated incidence of 1 : 40 000, characterized by hepatic, ophthalmic, and neuropsychiatric symptoms from excess copper accumulation. Despite many known anesthetic problems, there are very few reports of WD for procedures under anesthesia.
| Case report|| |
A 28-year-old female, American Society of Anesthesiologists-II, weighing 45 kg, presented with complaints of fever with chills and dizziness on and off for the last 3 months. On admission, she was investigated and found to have anemia and thrombocytopenia. On examination, the patient was pale and had a palpable huge spleen. Past history revealed a diagnosis of WD 15 years ago, and she was started on oral penicillamine and zinc acetate twice a day. Her neuropsychiatric status and ophthalmic examination were normal. Serum ceruloplasmin levels were low at that time (18 mg/dl). She had a history of full-term normal delivery 1 year back, when 4 U of platelets were infused in view of thrombocytopenia. No history of bleeding from any site was noted. On examination, the patient was pale and had a palpable liver and a huge spleen (hypersplenism). Her hemoglobin level was 8.4 g/dl and platelet count was 70 000/mm3. Other investigations including liver functions and coagulation profile were normal. Ultrasonography of the abdomen revealed liver parenchymal disease with a splenic span of 20 cm. The patient was posted for splenectomy under general anesthesia. After confirming the nil by mouth status (8 h) and a written informed consent, the patient was premedicated with glycopyrrolate 0.2 mg intramuscularly half an hour before the procedure, followed by ondansetron 4 mg, midazolam 1 mg, and fentanyl 50 μg intravenously. After preoxygenation, induction was carried out using propofol 100 mg and atracurium 15 mg intravenously. The patient was intubated with a 7.5 mm internal diameter cuffed endotracheal tube and maintained on oxygen 50%, nitrous oxide 50%, and isoflurane (0.4–0.6%, minimal alveolar concentration 0.6) as inhalational agents with intermittent positive pressure ventilation on Bain circuit (manual ventilation) using atracurium as the muscle relaxant. The intraoperative blood loss was around 1.5 l [permissible blood loss was around 200 ml and the patient was infused with 2 U of whole blood, 4 U of platelets, and 4 U of fresh frozen plasma after clamping the splenic port (splenic vessels)].
Intraoperative pulse, blood pressure, oxygen saturation, and end-tidal carbon dioxide were well maintained throughout the procedure. At the end of the surgery, the patient was reversed with glycopyrrolate 0.4 mg and neostigmine 2.5 mg intravenously after return of tone, power, and reflexes.
| Discussion|| |
The normal estimated total body copper content is 50–100 mg. Copper is an important component of several metabolic enzymes. Around 50–75% of intestinal copper is absorbed and then transported to hepatocytes. This pathway is intact in WD patients. After copper reaches hepatocytes, it is incorporated into copper-containing enzymes and copper-binding proteins, including ceruloplasmin, a serum ferroxidase. In WD, the processes of incorporation of copper into ceruloplasmin and excretion of excess copper into bile are impaired. The transport of copper by the copper-transporting P-type ATPase is defective in this disease.
WD, also known as hepatolenticular degeneration, is caused by reduction in the synthesis of the copper transporter protein ceruloplasmin. Owing to ceruloplasmin deficiency, there is failure of excretion of copper into bile and it accumulates in body tissues leading to major hepatic and neurological involvement . Hepatic involvement after excess copper deposition leads to chronic liver disease and cirrhosis, which may alter metabolism and excretion of anesthetic agents. The neurological effects include movement disorders, with abnormalities of speech, tremor, incontinence, and dystonia.
General, subarachnoid, and epidural anesthesia have all been reported in patients with WD. Regional anesthesia is safe if possible in these cases as peripheral nerves are not affected . Neuraxial block can be considered after ruling out coagulopathy and thrombocytopenia, because of less use of drugs and minimal effects on vital organs . However, as our patient needed splenectomy, general anesthesia was a better option. Decrease in total hepatic blood flow, which occurs normally during general anesthesia, the effects of anesthetics that are toxic to the liver, decreased blood pressure during anesthesia, and decrease in tissue perfusion as a result of surgery may further disrupt hepatic function that is already impaired in WD and cause hepatic injury . Impaired hepatic function can adversely affect the absorption, distribution, metabolism, and excretion of anesthetics, muscle relaxants, analgesics, and sedatives. Volatile anesthetics are cardiac depressants, reducing cardiac output, mean arterial pressure, and liver blood flow. Further, inducing agents and inhalational agents may interfere with central nervous system function and may exacerbate neurological and behavioral problems postoperatively . Isoflurane, an inhaled anesthetic that increases hepatic blood flow, is a safe choice in these cases.
Hypnotic sedatives may have delayed or incomplete metabolism exacerbating postoperative neurological and psychiatric problems. A case of WD diagnosed by the occurrence of acute neuropsychiatric symptoms after general anesthesia has been reported ,.
Hypnotic and sedative drugs interfere significantly with the central nervous system and may, therefore, exacerbate neurological and psychiatric problems in the postoperative period. However, there was no known preoperative neuropsychiatric symptom in our patient and it was not observed postoperatively. There is increased sensitivity to the sedative and cardiorespiratory depressant effects of propofol; however, clearance is not significantly impaired by liver disease.
In this study, we used propofol as an inducing agent without any significant side-effect. Fentanyl, a narcotic agent that is least affected by liver function, is a good option as a sedative analgesic . The metabolism of suxamethonium may be slowed because of reduced pseudocholinesterase. Patients may be more sensitive to neuromuscular relaxants from reduced muscle functioning secondary to the disease, elevated blood copper levels interfering with neuromuscular transmission, or the use of d-penicillamine. Atracurium, which we used, is considered as the first choice because it relies on neither the liver nor the kidneys for excretion. Treatment of this disease is lifelong and even a short-term, temporary break in pharmacological therapy could result in copper accumulation .
Therefore, medical treatment should be re-instated as soon as possible postoperatively. Hence, we re-started medical treatment with previous medications as soon as we ensured that oral intake would not cause a problem.
Copper is a renal toxin that can induce renal failure by a direct effect on the kidneys or indirectly through hemoglobinuria from intravascular hemolysis and myoglobinuria. In a prospective study of patients with WD, cardiac copper accumulation was reported to cause left ventricular parietal thickening with an increased prevalence of concentric left ventricular remodeling and relatively high frequency of benign supraventricular tachycardias and extrasystolic beats . WD may rarely present as respiratory failure from muscle weakness or hypoxemia from restrictive defects secondary to tense ascites and/or pleural effusions or from ventilation perfusion mismatches associated with liver failure .
Hepatopulmonary syndrome and portopulmonary hypertension are pulmonary vascular disorders that occur in patients with severe liver disease and/or portal hypertension. Our patient was on regular therapy and did not show any major organ involvement related to the disease.
As anesthesiologists we must therefore have thorough knowledge of the effects of copper load on various organ systems and how the chronic drug therapy for WD can affect the anesthetic outcome.
Thus, this case of WD, rarely taken up for surgery, posted for splenectomy under general anesthesia was managed uneventfully after knowing the problems that copper load can pose for anesthetic management.
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Conflicts of interest
There are no conflicts of interest.
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