|Year : 2008 | Volume
| Issue : 4 | Page : 443
Refractory Hypotension after Tourniquet Deflation in a Patient on Chronic Clomipramine Therapy
Pradeep Govil1, P. N. Kakar2, Atul Kishore Kapoor3, Ankit Sharma3, Deepak Govil1, Deep Arora4
1 Consultant Anaesthesia, Department of Anaesthesia and Pain Management, Max Super Specialty Hospital, Saket, New Delhi-110017, India
2 Director, Anaesthesia and Pain Medicine, Max Healthcare, Department of Anaesthesia and Pain Management, Max Super Specialty Hospital, Saket, New Delhi-110017, India
3 Jr. Consultant Anaesthesia, Department of Anaesthesia and Pain Management, Max Super Specialty Hospital, Saket, New Delhi-110017, India
4 Senior Consultant, Anaesthesia and Pain Medicine, Max Superspecialty Hospital, New Delhi, India
|Date of Acceptance||24-May-2008|
|Date of Web Publication||19-Mar-2010|
Department of Anaesthesia and Pain Management, Max Super Specialty Hospital, Saket, New Delhi-110017
Source of Support: None, Conflict of Interest: None
Treatment of intraoperative hypotension in a patient on chronic tricyclic antidepressant therapy(TCA) is controversial. Evidence based guidelines for the management of psychotropic drugs during perioperative period are lacking. We present a patient who was subjected to bilateral total knee replacement under combined spinal epidural anaesthesia. She developed refractory hypotension after release of tourniquet and responded only to large dosage of norepinephrine along with acid base correction. We believe that chronic TCA therapy led to depleted catecholamine reserves and down regulation of its receptors. Release of tourniquet led to metabolic acidosis and subsequently increased free clomipramine concentration in blood leading to severe refractory hypotension.
Keywords: Tricyclic antidepressants, hypotension, clomipramine, tourniquet deflation, combined spinal epidural anaesthesia
|How to cite this article:|
Govil P, Kakar PN, Kapoor AK, Sharma A, Govil D, Arora D. Refractory Hypotension after Tourniquet Deflation in a Patient on Chronic Clomipramine Therapy. Indian J Anaesth 2008;52:443
|How to cite this URL:|
Govil P, Kakar PN, Kapoor AK, Sharma A, Govil D, Arora D. Refractory Hypotension after Tourniquet Deflation in a Patient on Chronic Clomipramine Therapy. Indian J Anaesth [serial online] 2008 [cited 2020 Jan 22];52:443. Available from: http://www.ijaweb.org/text.asp?2008/52/4/443/60660
| Introduction|| |
Major unipolar depression is one of the multiple co morbidities in geriatric age group and has been forecasted to be the second largest cause of death in 2020  . Providing anaesthesia and analgesia to these patients had been a unique challenge to the anaesthesiologists in past due to major drug interactions of antidepressants with anaesthetic drugs used.
Due to emergence of newer drugs for treatment of depression, there has been lack of awareness and preparedness for an untoward refractory hypotension that may or may not occur. Hypotension is known in patients undergoing treatment with tricyclic antidepressants (TCA). Severe hypotension is rare with therapeutic doses of TCA  . Scanty review material is available pertaining to this issue .Literature search revealed only a few case reports of hypotension after induction of anaesthesia , . Treatment of hypotension in such patients is controversial, while some authors recommend reduced doses of phenyhephrine ,, , others suggest higher doses of noradrenaline  . Evidence based guidelines for the management of psychotropic drugs during perioperative period are lacking.
We present a patient who was subjected to bilateral total knee replacement under combined spinal epidural anaesthesia. She developed hypotension which worsened after release of tourniquet and responded only to large dosage of norepinephrine along with acid base correction.
| Case report|| |
A 54 year old lady (BMI 32) was scheduled for bilateral total knee replacement for osteoarthritis both knees. Her medical history was significant for depression from last 20years managed with clomipramine 25mg OD, history of Type 2 diabetes mellitus(DM) from last 15 years, diet controlled and 4 years history of hypertension that had been controlled with a combination of amlodipin 5mg and atenolol 50mg OD.
The preoperative biochemical and hematological profile was within normal limits. Electrocardiogram was unremarkable and echocardiogram revealed normal ventricular size, function, and left ventricular ejection fraction of 65%. Patient was given clearance for surgery under ASA classification II and combined spinal epidural anaesthesia was planned.
Patient was premedicated with ranitidine150mg and alprazolam 0.25mg the night before surgery and it was repeated on the morning of surgery with the medications on which patient was already on. .
The patient's preoperative blood pressure was 120/70 mmHg, and her heart rate was 72 beats /min. She was visibly anxious. Routine monitoring (ECG, NIBP, SpO 2 ) was started. Pethidine 30mg and midazolam1mg was given intravenously. Oxygen via mask at 3l.min -1 was started.
Preloading was done with 15ml.kg -1 0.9% saline. Combined spinal epidural was given in left lateral position under all aseptic precautions. Local infiltration of L3-L4 interspace was done with 2% lidocaine. Epidural space was reached using 16 G tuohy needle by loss to air resistance technique. Sub-arachnoid block was given using 26 G pencil point needle using needle through needle technique.2.8ml of bupivacaine 0.5% (heavy) given and 16 G epidural catheter was inserted and fixed at 10cm .No drug was given through epidural catheter.
Patient was kept in supine position for surgery, Hypotension (BP 90/50 mmHg) was observed. Mephentermine was given intravenously in 3mg increments. Blood pressure stabilized to 100/60 mmHg. Surgeon cleaned and draped the part and left sided tourniquet was inflated for left sided total knee replacement. Patient was conscious and comfortable and was responding to commands. Propofol infusion 6ml.hr -1 (60mg.hr -1 ) was started for sedation as the normal anaesthesia protocol.
Left sided total knee replacement took 64 minutes. Tourniquet was deflated after tight compression dressing and after clamping the drain (as normal surgical protocol). Following tourniquet deflation, the blood pressure dropped to 70/50mmHg. Haemodynamic stabilization could be achieved after using 30mg of mephentermine in incremental doses and intravenous fluids. It was realized that higher doses of mephentermine had been used to achieve haemodynamic stabilization, so propofol infusion was discontinued.
After exsanguination of the other limb (right lower limb) tourniquet was inflated and surgery was initiated on right knee. 2.5 liters of crystalloids and colloids were administered and mean arterial blood pressure of patient remained 70-80 mm Hg throughout right limb surgery.
Tourniquet of second side (right lower limb) was deflated after 58 minutes. Blood pressure again decreased to 78/50 mmHg. Mephentermine and intravenous fluids were given in attempt to achieve mean arterial blood pressure above 65mmHg. Repeated incremental doses of mephentermine were given but hypotension was refractory to the use of mephentermine and dopamine infusion at the rate of 5µg.kg -1 .min -1 started and then incrementally increased to 10µg.kg1 .min -1 . Dexamethasone 16mg was administered intravenously. Inspite of administration of such high doses of dopamine, systolic blood pressure remained between 75-85 mmHg.
Systemic examination of patient revealed bilateral basal crepts, more on left side. ABG analysis done intraoperatively revealed pH 7.244, pCO 2 31.3 mmHg, pO 2 64.9mmHg, HCO 3- 18.3 mmol/l and base deficit 5.6 mmol.l -1 . Sodium bicarbonate 75ml (7.5%) was given intravenously. Patient was catheterized and total urine output found to be 150ml. Morphine 6mg and frusemide 20mg was given intravenously.
Arterial line was placed to monitor arterial blood pressure. On table electrocardiography and echocardiography was performed. ECG was normal and echocardiography showed good L.V. function, no regional wall motion abnormality, empty chambers, LVEF 65% and mildly raised pulmonary artery systolic pressure.
Central venous pressure line was inserted which revealed CVP of 4cm H 2 O. Additional intravenous fluids were given but of no avail.
Noradrenaline infusion was started at rate of 0.05µg.kg -1 .min -1 and incrementally increased to 0.2 µg.kg1 .min -1 . Pulse rate gradually increased from 70/min (preoperative) to 100 beats/min. Blood pressure stabilized to 100/60 mmHg on dopamine 10 µg.kg -1 .min -1 and noradrenaline 0.2 µg.kg -1 .min -1 .
Patient was shifted to high dependency unit(HBD). On arrival to HDU, patient was conscious and oriented, pulse 98/ min, BP 98/56 mmHg, respiratory rate 20/ min and SpO2 97% on oxygen via mask. Bilateral basal crepts were auscultated. Patient was still on dopamine and noradrenaline infusion. Motor power in both lower limbs was 2/5 and patient was given morphine in increments of 3mg IV for pain relief.
Second ABG analysis in HDU showed pH 7.279, pCO 2 43.6 mmHg, pO2 64.3mmHg, HCO 3 - 19.8 mmol/l and base deficit 6.2mmol. Sodium bicarbonate 100ml (7.5%) was given intravenously. Patient received 120mg of frusemide in HDU over 6 hours in increments of 20mg given intravenously.
Blood pressure stabilized rapidly after correction of acid base status (as revealed by third ABG analysis, pH 7.454, pCO 2 35.8 mmHg, pO 2 69.6mmHg, HCO 3 24.7 mmol/l, Base Excess 1.6mmol/l ) and dopamine and noradrenaline infusion was tapered off over 15 hours. Patient remained comfortable throughout except for pain for that morphine 3mg increments were given intravenously. Epidural infusion was not used for postoperative analgesia.
All patient parameters were found to be normal on the next day and patient was transferred to the ward.
| Discussion|| |
Significant hypotension with routine doses of TCA is uncommon . Circulatory shock like situation is seen normally with TCA overdose  .
Clomipramine inhibits norepinephrine and serotonin uptake into central nerve terminals, possibly by blocking the membrane-pump of neurons, thereby increasing the concentration of transmitted monoamines at receptor sites  .
Chronic TCA administration may also lead to hypotension by blocking norepinephrine reuptake into presynaptic nerve terminals. Desmethylclomipramine, the principal metabolite of clomipramine blocks norepinephrine and serotonin reuptake  .This may lead to depleted catecholamine reserve in nerve terminals. This can limit compensatory haemodynamic response , .
Chronic exposure to post synaptic adrenergic receptors to the high concentration of epinephrine produced by reuptake inhibition may cause down regulation of these receptors leading to decreased responsiveness to catecholamine  .
Clomipramine is extensively bound to plasma proteins and has large volume of distribution. Administration of clomipramine to patient taking other drugs that are highly bound to proteins i.e., warfarin, digoxin may cause an increase in plasma concentration of these drugs, potentially resulting in adverse effect, conversely, adverse reaction may result from the displacement of protein bound clomipramine to other highly bound drugs.
Metabolic acidosis also leads to decreased protein binding of clomipramine, leading to increased concentration of free drugs and can mimic symptoms of TCA overdose. Hypotension caused by TCA overdose may result from myocardial depression or peripheral vasodilatation. This is attributed to lactic acidosis, which impairs myocardial sodium conduction. Iwama et al stated that after tourniquet deflation, arterial blood lactate levels are increased at all times  .
Our patient did not have any preoperative and post operative orthostatic hypotension, but suffered from severe refractory intraoperative hypotension not responding to fluids and mephentermine.
We considered several mechanisms.
High spinal block was ruled out, by checking the level of block and that initially patient responded to the regular doses of mephentermine, hypotension did persist after the effect of subarachnoid block was over. An insufficient endogenous steroid response to stress was excluded because amount of dexamethasone given during anaesthesia should have been sufficient to prevent hypotension. Hypovolemia was ruled out as patient was initially preloaded and surgery was conducted under tourniquet.
We did not encounter any signs of allergic or anaphylactic drug reaction in our patient.
We noted that after release of tourniquet, high doses of dopamine were required to manage hypotension. Then hypotension even became refractory to these drugs and ultimately high doses of norepinephrine were able to raise blood pressure.
Arterial blood gas analysis done during intraoperative period showed metabolic acidosis, which could be due to the release of metabolites at the time of reperfusion of lower limb. Metabolic acidosis also decreases protein binding of clomipramine leading to increased clomipramine concentration and this may have mimicked situation such as TCA poisoning.
Only after correction of acidosis and infusion of noradrenaline, blood pressure stabilized.
We believe that chronic TCA therapy could have led to depleted catecholamine reserves and down regulation of its receptors. Release of tourniquet led to metabolic acidosis and subsequently increased free clomipramine concentration in blood leading to severe refractory hypotension. This can be explained on the basis of study by Wilgis which describes venous pH response to tourniquet ischemia  .
This patient's hypotension was ultimately treatedwith high doses of norepinephrine, sodium bicarbonate and I.V fluids. Various authors recommend same line of management for treatment of TCA overdose induced circulatory collapse , .
The use of dopamine in the management of hypotension has been advocated, but the pressor effect of this indirectly acting inotrope may be diminished in TCA overdose due to depleted level of noradrenaline.
The AHA's recommendation for managing hypotension resulting from TCAs is to first administer 1 l of intravenous saline. If this fails, the next step is to increase the serum pH to 7.5-7.55. Patients with refractory hypotension may then be treated with dopamine or norepinephrine infusion  .
Abrupt withdrawal of tricyclic antidepressants (TCAs) is linked with insomnia, nausea, irritability, and agitation. TCAs inhibit the reuptake of biogenic amines in the CNS and peripheral nervous system, which can predispose patients to cardiac arrhythmias.
Recommendations regarding the perioperative management of TCAs are variable. One review recommends continuing TCAs throughout the perioperative period  . Others suggest tapering the dosage and discontinuing the agents 1-2 weeks before surgery in patients taking low dosages or thought to be at high risk for perioperative arrhythmia , .
Huyse et al on the basis of a systematic analysis of the available literature guided by the formulated perioperative risks formulated a proposal for the perioperative management of psychotropic drugs. Patients who use TCAs can have serious drug interactions, with increased physical risks, including withdrawal, and therefore should qualify for American Society of Anesthesiologists (ASA) Classification 3. As there is physical risk, they require discontinuation, but due to the possibility psychiatric relapse and recurrence, intensive and integrated anaesthetic/psychiatric management should be planned  .
We conclude that the less potent sympathomimetics may not effectively manage hypotension in patients receiving long term TCA therapy because of depleted catecholamine stores and desensitizes adrenergic receptors.
Furthermore if tourniquet has to be used in these patients, arterial blood gas analysis should be done promptly after release of tourniquet and patient should be alkalinized with sodium bicarbonate to prevent TCA toxicity.
In these patients potent directly acting sympathomimetic may be the only effective management of hypotension.
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