Indian Journal of Anaesthesia  
About us | Editorial board | Search | Ahead of print | Current Issue | Past Issues | Instructions
Home | Login  | Users Online: 2696  Print this pageEmail this pageSmall font sizeDefault font sizeIncrease font size    




 
CASE REPORT
Year : 2008  |  Volume : 52  |  Issue : 4  |  Page : 443 Table of Contents     

Refractory Hypotension after Tourniquet Deflation in a Patient on Chronic Clomipramine Therapy


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 Acceptance24-May-2008
Date of Web Publication19-Mar-2010

Correspondence Address:
Pradeep Govil
Department of Anaesthesia and Pain Management, Max Super Specialty Hospital, Saket, New Delhi-110017
India
Login to access the Email id

Source of Support: None, Conflict of Interest: None


Rights and PermissionsRights and Permissions
 

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 Jul 16];52:443. Available from: http://www.ijaweb.org/text.asp?2008/52/4/443/60660


   Introduction Top


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 [1] . 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 [2] . Scanty review material is avail­able pertaining to this issue .Literature search revealed only a few case reports of hypotension after induction of anaesthesia [3],[4] . Treatment of hypotension in such patients is con­troversial, while some authors recommend reduced doses of phenyhephrine [5],[6],[7] , others suggest higher doses of noradrenaline [4] . 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 Top


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 Top


Significant hypotension with routine doses of TCA is uncommon [8]. Circulatory shock like situation is seen normally with TCA overdose [9] .

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 [10] .

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 [11] .This may lead to depleted catecholamine reserve in nerve terminals. This can limit compensatory haemodynamic response [12],[13] .

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 [11] .

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 [14] .

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 [15] .

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 [16],[17] .

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 [18] .

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 [19] . 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 [20],[21] .

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 [22] .

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.

 
   References Top

1.Murray CJL and Lopez AD. Global mortality, disability, and the contribution of risk factors: Global Burden of Disease Study. Lancet 1997; 349:1436-42.  Back to cited text no. 1      
2.Glassman AH. Cardiovascular effects of antidepressant drugs. Updated. Int Clin Psychopharmacol 1998; 13: S25-­30.  Back to cited text no. 2  [PUBMED]    
3.Sprung J, Schoenwald PK, Levy P, Krajewski LP. Treat­ing intraoperative hypotension in a patient on long­term tricyclic antidepressants: A case of aborted aortic surgery. Anesthesiology 1997; 86: 990-2  Back to cited text no. 3      
4.Malan TP Jr., Nolan PE Jr., Lichtenthal PR, et al. Severe, refractory hypotension during anaesthesia in a patient on chronic clomipramine therapy. Anesthesiology 2001; 95: 264-6.  Back to cited text no. 4      
5.Stoelting RK, Dierdorf SF, McCammon RL. Anesthesia and Coexisting Disease. New York, Churchill Livingstone, 1988: 717-28.  Back to cited text no. 5      
6.Gilles BS. Anesthesia outside the operating room, Clini­cal Anesthesia. Edited by Barash PG, Cullen BF, Stoelting RS. Philadelphia, JB Lippincott, 1992:1465-77.  Back to cited text no. 6      
7.Stoelting RK. Pharmacology and Physiology in Anes­thetic Practice. Philadelphia, JB Lippincott, 1987: 347-­64.  Back to cited text no. 7      
8.Cummins RO. Textbook of Advanced Cardiac Life Sup­port. Dallas, American Heart Association, 1994.  Back to cited text no. 8      
9.Shannon M, Liebelt EL. Toxicology reviews: Targeted management strategies for cardiovascular toxicity from tricyclic antidepressant overdose: The pivotal role for alkalinization and sodium loading. Ped Emerg Care 1999; 14: 293-8.  Back to cited text no. 9      
10.Hyttel J. Serotonin uptake inhibitors, Serotonin: From Cell Biology to Pharmacology and Therapeutics. Edited by Vanhoute PM, Paoletti R, Brunello N, Maggi FM. Norwell, MA, Kluwer Academic Publishers, 1989, 459-64.  Back to cited text no. 10      
11.Banerjee SP, Kung LS, Riggi SJ, Chanda SK . Develop­ment of beta-adrenergic receptor subsensitivity by an­tidepressants. Nature 1977; 268: 455-6 .  Back to cited text no. 11  [PUBMED]    
12.Newton EH, Shih RD, Hoffman RS. Cyclic antidepres­sant overdose: a review of current management strate­gies. Am J Emerg Med 1994; 12: 376-9 .  Back to cited text no. 12  [PUBMED]  [FULLTEXT]  
13.Shannon M, Merola J, Lovejoy FH. Hypotension in se­vere tricyclic antidepressant overdose. Am J Emerg Med 1988; 6: 439-42.  Back to cited text no. 13      
14.Iwama H, Keneko T, Ohmizo H et al. Circulatory, respira­tory and metabolic changes after thigh tourniquet re­lease in combined epidural- propofol anaesthesia with preservation of spontaneous respiration. Anaesthesia 2002;57:588-92.  Back to cited text no. 14      
15.Wilgis EFS. Observations on the effects of tourniquet ischemia. J Bone Joint Surg Am 1971; 53:1343-1346.  Back to cited text no. 15      
16.Hoffman JR, McElroy CR. Bicarbonate therapy for dysrrhythmia and hypotension in tricyclic antidepressant overdose. West J Med 1981; 134:60-4.  Back to cited text no. 16  [PUBMED]  [FULLTEXT]  
17.Teba L, Schiebel F, Dedhia HV, Lazzelli VA. Beneficial effect of norepinephrine in the treatment of circulatory shock caused by tricyclic antidepressants. Am J Emer Med 1995; 6:566-8.  Back to cited text no. 17      
18.Sprung J, Schoenwald PK: Reply. American Heart As­sociation Recomendations for treating tricyclic antide­pressant-induced hypotension. Anesthesiology 1997 ;87: 1260.  Back to cited text no. 18      
19.Saber W. Perioperative medication management:A case­based review of general principles Cleveland Clinic J Of Medicine 2006; 73(S 1): S82-S87.  Back to cited text no. 19      
20.Cohn SL. Perioperative medication management. Ameri­can College of Physicians, Physicians' Information and Education Resource. Available by subscription at: http://pier.acponline.org.  Back to cited text no. 20      
21.Kraft WK, Diemer G. Managing medication in the perioperative period. In: Merli G, Weitz H, eds. Medical Management of the Surgical Patient. 3rd ed. Philadel­phia, Pa: Saunders [in press].  Back to cited text no. 21      
22.Huyse JF, Touw DJ, Schijndel RSV. Psychotropic drugs and the perioperative period: A proposal for a guideline in elective surgery. Psychosomatics 2006; 47:8-22.  Back to cited text no. 22      




 

Top
 
  Search
 
    Similar in PUBMED
   Search Pubmed for
   Search in Google Scholar for
 Related articles
    Access Statistics
    Email Alert *
    Add to My List *
* Registration required (free)  

 
  In this article
    Abstract
    Introduction
    Case report
    Discussion
    References

 Article Access Statistics
    Viewed2262    
    Printed85    
    Emailed0    
    PDF Downloaded230    
    Comments [Add]    

Recommend this journal