- Email: [email protected]
A case of refractory intraoperative hypotension treated with vasopressin infusion
Journal of Clinical Anesthesia (2008) 20, 139–142
Case report
A case of refractory intraoperative hypotension treated with vasopressin infusion Adam D. Wheeler MD (Resident)a , John Turchiano MD (Instructor)b , Joseph D. Tobias MD (Vice-Chairman and Professor)a,b,⁎ a
Department of Pediatrics, University of Missouri, Columbia, MO, USA Department of Anesthesiology, University of Missouri, Columbia, MO 65212, USA
b
Received 30 January 2007; revised 28 June 2007; accepted 29 June 2007
Keywords: Intraoperative hypotension; Vasopressin infusion
Abstract A 56-year-old man, treated with an angiotensin II receptor antagonist for hypertension, presented for placement of a cochlear implant during general anesthesia. Intraoperatively, there was profound hypotension that was resistant to decreasing the anesthetic depth, fluid administration, as well as bolus doses of phenylephrine, ephedrine, and epinephrine. Hypotension was eventually successfully treated with a vasopressin infusion (0.06 U/min). Vasopressin may be a useful agent in such scenarios because its effect is not dependent on either adrenergic or angiotensin receptors, both of which may be affected by angiotensin II receptor antagonists. © 2008 Elsevier Inc. All rights reserved.
1. Introduction Hypotension during general anesthesia is generally easily treated by decreasing the depth of anesthesia and the administration of fluid. When needed, catecholamines, including phenylephrine, ephedrine, or epinephrine, are used due to their rapid onset and predictable hemodynamic response. Patients taking angiotensin-converting enzyme (ACE) inhibitors and angiotensin II receptor blocking agents preoperatively have a higher incidence of hypotension, more profound hypotension, and decreased responsiveness to exogenous catecholamines [1,2]. Although there
⁎ Corresponding author. Department of Anesthesiology; University of Missouri, Columbia, MO 65212, USA. Tel.: +1 573 882 7168; fax: +1 573 882 2226. E-mail address: [email protected] (J.D. Tobias). 0952-8180/$ – see front matter © 2008 Elsevier Inc. All rights reserved. doi:10.1016/j.jclinane.2007.06.023
are data to support the withholding of ACE inhibitors and angiotensin II receptor blocking agents on the morning of surgery so as to lessen the risk of hypotension [3,4], it is not a universally accepted practice. At our institution, patients taking these agents are generally instructed to take their usual morning dose. We present a patient who had recently been started on an angiotensin II receptor blocking agent, who experienced profound hypotension after induction of general anesthesia. The hypotension was refractory to conventional therapy including fluid administration and pharmacologic treatment with ephedrine, phenylephrine, and epinephrine. The case report emphasizes the potential for refractory hypotension associated with angiotensin II receptor blockers and discusses treatment with vasopressin agonists [1,2,5,6]. We also discuss potential mechanisms to explain the apparent catecholamine resistance in this patient population.
140
A.D. Wheeler et al.
2. Case report Review of this patient's hospital records and presentation of this case report were approved by the institutional review board of the University of Missouri, Columbia. The patient was a 56-year-old, 94-kg, 175-cm man, who presented for a cochlear implant for the treatment of hearing loss due to excessive noise exposure. His medical history was positive for hypertension, treated with hydrochlorothiazide 12.5 mg daily and irbesartan, an angiotensin II receptor blocker, 150 mg daily. There was no other history of heart disease. During his initial preoperative evaluation, his blood pressure (BP) was 168/107 mmHg, and he was referred back to his primary care physician (PCP) for better management of the hypertension. During the return visit to his PCP, his BP was 140/88 mmHg, and the irbesartan was increased to 300 mg daily because the patient did not tell the PCP that he had not been taking the 150-mg dose, which had been prescribed previously. This fact was not discovered until after the surgical procedure. On further investigation, it was learned that he had taken the 150-mg dose of irbesartan for only two days before the dose increase. He took the higher dose (300 mg) for 6 days before surgery. On the day of surgery, the
Table 1
patient was fasted (except for medications) for 6 hours. His BP was 145/98 mmHg in the preoperative holding area. He had taken the usual dose of both hydrochlorothiazide and irbesartan. A peripheral 18-gauge intravenous (IV) cannula was placed on the dorsum of the hand and midazolam 2 mg was administered. The patient was transported to the operating room (OR) where standard ASA monitors (temperature, noninvasive BP, 5-lead continuous electrocardiogram, end-tidal carbon dioxide, pulse oximetry, and precordial stethoscope) were placed. An IV fluid bolus of 500 mL of Ringer's lactate was administered, followed by induction of general anesthesia with fentanyl 50 μg, lidocaine 100 mg, propofol 250 mg, and succinylcholine 120 mg. Lidocaine was used because of the patient's history of hypertension in an attempt to blunt the response to intubation. Sevoflurane (inspired concentration 2%) was started before direct laryngoscopy and endotracheal intubation. Table 1 lists the subsequent hemodynamic parameters (heart rate and BP) and subsequent therapy. When ephedrine, phenylephrine, and epinephrine failed to increase BP, IV vasopressin (0.4 units) was administered. The dose was increased to 2 U every 10 minutes as it allowed for fewer doses, but BP remained labile, with systolic BP (SBP) ranging from 75 to 115 mmHg.
Intraoperative hemodynamic parameters and subsequent therapy
Time after intubation (min)
BP (mmHg)
Heart rate (bpm)
Treatment (IV)
−1 4
138/92 60/40
72 63
None Phn 100 μg, fluid bolus initiated, inhaled sevoflurane decreased from 2% to 0.5%
7 10 13 16
64/32 80/42 62/42 65/42
65 46 54 54
Phn 200 μg, Eph 10 mg Eph 20 mg, EPI 10 μg Eph 20 mg, EPI 20 μg, Phn 200 μg Eph 20 mg, EPI 20 μg, Phn 500 μg
19 21 24
120/54 70/48 90/54
46 65 75
45
75/38
55
90
83/35
64
Eph 20 mg, EPI 10 μg Phn 200 μg, ketamine 100 mg Phn 100 μg, ketamine 50 mg (two doses separated by 10 min) Phn 100 μg, Eph 20 mg, ketamine 50 mg (three doses separated by 10 min) Vasopressin 0.4 units
98 104 107 121
90/54 90/58 106/65 92/61
65 64 72 74
180 210
98/57 88/54
73 76
Vasopressin 0.4 units Vasopressin two units None Vasopressin two units every 15 min (5 doses) Vasopressin infusion at 0.04 U/min Vasopressin infusion increased to 0.06 U/min
Comment
Total 4 L of Ringer's lactate given during first 1.5 hrs. Radial pulses were faint but palpable. A different NIBP cuff was placed on right lower extremity, yielding similar results.
Patient coughing. BIS b 60 at this time and throughout case.
Surgical stimulation begins. Patient moving in response to surgical stimulation. BIS 50-56.
Propofol (50 μg/kg/min) and ketamine (3 mg/kg/hr) infusion started.
BP maintained without further intervention. Infusion stopped when patient awakened from general anesthesia.
Phn = phenylephrine; NIBP = noninvasive BP; Eph = ephedrine; EPI = epinephrine; BIS = bispectral index.
ARB and vasopressin To achieve steadier control of BP, a vasopressin infusion was started at 0.04 U/min and increased to 0.06 U/min, which maintained BP at 90 to 110/40 to 110/80 mmHg. Vasopressin was administered for a total of 165 minutes, with a continuous infusion given for 75 minutes. The entire case lasted 5 hours. Urine output during the case was 1.1 mL/kg/hr before vasopressin and 1.4 mL/kg/hr during vasopressin use. At the conclusion of the case, the propofol and ketamine infusions were discontinued and the vasopressin infusion was stopped when the patient awakened. The patient denied recall. There was no further hemodynamic instability. He was discharged home the following day and was doing well at a follow-up visit 1 week later.
3. Discussion Patients receiving medications that attenuate the reninangiotensin system in the preoperative period are known to have more frequent and more severe episodes of hypotension after induction of anesthesia [1,2]. After anesthetic induction, inhibition of the sympathetic nervous system by anesthetic agents results in alterations in cardiovascular function and BP that are usually attenuated by the angiotensin system [7]. Patients taking agents that antagonize this system are thus left without a key compensatory mechanism. Catecholamine resistance in patients taking ACE inhibitors and angiotensin II receptor blockers has been reported in the literature [8-10]. Eyraud et al [8] reported that 10 of 51 patients taking these agents had hypotension refractory to three doses of a catecholamine, and that these patients responded to the vasopressin agonist, terlipressin. In a cohort of adult patients undergoing cardiac surgery and cardiopulmonary bypass, Oh et al [9] reported that patients taking angiotensin II receptor blockers (candesartan, losartan, irbesartan, or valsartan) required higher doses of phenylepherine to maintain BP. Two animal studies provide some insight into a cellular mechanism that may explain the catecholamine-resistant hypotension noted in our patient. Godínez-Hernández et al [11] showed that rats treated with captopril had a decreased density of α1D-adrenergic receptors in the aorta. In addition, when phenylephrine was administered, there was a 60% decrease in the response of aortic contractility when compared with rats not treated with captopril. Godínez-Hu et al [12] showed that treatment of rat vascular smooth muscle cells with angiotensin II significantly increased the expression of α1D-adrenergic receptor messenger RNA when compared with cells not treated with angiotensin II. This effect was blocked by the administration of an angiotensin II receptor blocker. These studies suggest that vasopressin would be a logical alternative for the treatment of catecholamine-resistant hypotension because it depends neither on angiotensin nor the adrenergic receptors for its mechanism of action.
141 Vasopressin is a peptide hormone secreted by the hypothalamus in response to several stimuli, including decreased preload, increased plasma osmolarity, and decreased BP [12]. The primary functions of vasopressin include regulation of serum osmolarity and vascular tone. Vasopressin stimulates the V1 receptor, which is a G protein– coupled receptor, on vascular smooth muscle, thereby resulting in vasoconstriction. Use of the IV preparations (vasopressin, terlipressin) have been described for the treatment of hypotension in various clinical scenarios including hypotension refractory to catecholamines [5,6,13,14]. Terlipressin is also known as tricyl-lysinevasopressin. Its slow metabolism to the active lysinevasporessin provides for its longer half-life (6 hrs vs vasopressin's half-life of 6 min) [14]. Although most experience in the anesthesia literature has reported the use of terlipressin due to its longer half-life [1,2,8,13], this drug is not available at our institution. Therefore, we chose to use vasopressin, which is readily available in our ORs. Terlipressin has been well studied in patients with hypotension related to ACE inhibitors and angiotensin II receptor blockers. Meersschaert et al [15] randomized patients taking ACE inhibitors to receive ephedrine or terlipressin plus ephedrine for hypotension during general anesthesia. Patients receiving terlipressin in addition to ephedrine required less ephedrine (median dose of 3 vs 6 mg) to maintain normal BP. Boccara et al [16] randomized patients to receive terlipressin (intermittent 1 mg bolus doses) or a continuous infusion of norepinephrine in the treatment of ephedrine-resistant hypotension in patients receiving ACE inhibitors or angiotensin II receptor blockers during general anesthesia for carotid endarterectomy. Patients treated with terlipressin experienced a shorter duration of SBP measuring less than 90 mmHg. In addition, nonresponsiveness to therapy, defined as hypotension despite three boluses of terlipressin or three changes in the norepinephrine infusion rate, occurred in 0 of 10 patients treated with terlipressin versus 8 of 10 patients treated with norepinephrine. In our patient who failed to respond to multiple doses of various catecholamines, we noted a prompt response to the vasopressin bolus doses followed by maintenance of the BP with the vasopressin infusion. As previously mentioned, terlipressin is not available in our institution, although we would also postulate that in anesthetic practice, a continuous infusion of vasopressin may provide for more titratable control of BP than intermittent boluses of the longer-acting terlipressin. In addition, the anesthetic agent exacerbating hypotension is often quickly withdrawn at the conclusion of the case, which could result in rebound hypertension if terlipressin has been used. An important adverse effect of vasopressin agonists is the potential for hypoperfusion to “non-essential” tissues, with decreases in perfusion to the splanchnic and renal circulation [14,17], as the monitoring of urine output is important for ensuring adequate perfusion during the administration of vasopressin.
142 At the same time that we started vasopressin in our patient, we decreased the sevoflurane concentration and began IV anesthesia using a propofol-ketamine infusion. Although propofol likely results in greater myocardial depression than sevoflurane [18], in most patients, ketamine results in an increase in BP and cardiac output [19]. Ketamine was chosen to decrease the total dose of propofol and thereby limit propofol-related cardiovascular effects, including hypotension [20]. This combination was used in an attempt to achieve greater hemodynamic stability than sevoflurane alone and also ensure amnesia in a patient with hemodynamic instability. It is uncertain which role these agents played in the response to vasopressin. For the initial therapy for the hypotension, we chose to use intermittent doses of catecholamines rather than a continuous infusion because there was a minimal clinical response to the relatively high bolus doses of catecholamines including ephedrine, phenylephrine, and epinephrine. Given this lack of response, we did not think that there would be any advantage in using a continuous catecholamine infusion. In summary, patients receiving ACE inhibitors and angiotensin II receptor blockers can experience profound hypotension during general anesthesia. Although they are generally responsive to conventional therapy such as decreasing depth of anesthesia, administration of short-acting catecholamines, and fluids, refractory cases that necessitate additional therapy may occur. In such circumstances, vasopressin-receptor agonists may be effective. Given the potential for excessive vasoconstriction and decreases in endorgan perfusion, the dose of vasopressin should be titrated to maintain the lowest clinically acceptable BP level.
References [1] Brabant SM, Bertrand M, Eyraud D, Darmon PL, Coriat P. The hemodynamic effects of anesthetic induction in vascular surgical patients chronically treated with angiotensin II receptor antagonists. Anesth Analg 1999;89:1388-92. [2] Brabant SM, Eyraud D, Bertrand M, Coriat P. Refractory hypotension after induction of anesthesia in a patient chronically treated with angiotensin receptor antagonists. Anesth Analg 1999;89:887-8. [3] Comfere T, Sprung J, Kumar MM, et al. Angiotensin system inhibitors in a general surgical population. Anesth Analg 2005;100:636-44. [4] Bertrand M, Godet G, Meersschaert K, Brun L, Salcedo E, Coriat P. Should the angiotensin II antagonists be discontinued before surgery? Anesth Analg 2001;92:26-30.
A.D. Wheeler et al. [5] Jochberger S, Wenzel V, Dünser MW. Arginine vasopressin as a rescue vasopressor agent in the operating room. Curr Opin Anaesthesiol 2005;18:396-404. [6] Holmes CL, Patel BM, Russell JA, Walley KR. Physiology of vasopressin relevant to management of septic shock. Chest 2001; 120:989-1002. [7] Behnia R, Molteni A, Igic R. Angiotensin converting enzyme inhibitors: mechanisms of action and implications in anesthesia practice. Curr Pharm Des 2003;9:763-76. [8] Eyraud D, Brabant S, Nathalie D, et al. Treatment of intraoperative refractory hypotension with terlipressin in patients chronically treated with an antagonist of the renin-angiotensin system. Anesth Analg 1999;88:980-4. [9] Oh YJ, Lee JH, Nam SB, Shim JK, Song JH, Kwak YL. Effects of chronic angiotensin II receptor antagonist and angiotensin-converting enzyme inhibitor treatments on neurohormonal levels and haemodynamics during cardiopulmonary bypass. Br J Anaesth 2006;97:792-8. [10] Dendorfer A, Thornagel A, Raasch W, Grisk O, Tempel K, Dominiak P. Angiotenin II induces catecholamine release by direct ganglionic excitation. Hypertension 2002;40:348-54. [11] Godínez-Hernández D, Gallardo-Ortíz IA, López-Sánchez P, Villalobos-Molina R. Captopril therapy decreases both expression and function of alpha-adrenoceptors in pre-hypertensive rat aorta. Auton Autacoid Pharmacol 2006;26:21-9. [12] Hu ZW, Shi XY, Okazaki M, Hoffman BB. Angiotensin II induces transcription and expression of alpha 1-adrenergic receptors in vascular smooth muscle cells. Am J Physiol 1995;268(3 Pt 2): H1006-14. [13] Treschan TA, Peters J. The vasopressin system: physiology and clinical strategies. Anesthesiology 2006;105:599-612. [14] Delmas A, Leone M, Rousseau S, Albanese J, Martin C. Clinical review: vasopressin and terlipressin in septic shock patients. Crit Care 2005;9:212-22. [15] Meersschaert K, Brun L, Gourdin M, et al. Terlipressin-ephedrine versus ephedrine to treat hypotension at the induction of anesthesia in patients chronically treated with angiotensin converting-enzyme inhibitors: a prospective, randomized, double-blinded, crossover study. Anesth Analg 2002;94:835-40. [16] Boccara G, Ouattara A, Godet G, et al. Terlipressin versus norepinephrine to correct refractory arterial hypotension after general anesthesia in patients chronically treated with renin-angiotensin system inhibitors. Anesthesiology 2003;98:1338-44. [17] Dünser MW, Mayr AJ, Ulmer H, et al. Arginine vasopressin in advanced vasodilatory shock. A prospective, randomized, controlled study. Circulation 2003;107:2313-9. [18] De Hert SG, Cromheecke S, ten Broecke PW, et al. Effects of propofol, desflurane, and sevoflurane on recovery of myocardial function after coronary surgery in elderly high-risk patients. Anesthesiology 2003; 99:314-23. [19] Lippmann M, Appel PL, Mok MS, Shoemaker WC. Sequential cardiorespiratory patterns of anesthetic induction with ketamine in critically ill patients. Crit Care Med 1983;11:730-4. [20] Botero CA, Smith CE, Holbrook C, et al. Total intravenous anesthesia with a propofol-ketamine combination during coronary artery surgery. J Cardiothoracic Vasc Anesth 2000;14:409-15.
Case report
A case of refractory intraoperative hypotension treated with vasopressin infusion Adam D. Wheeler MD (Resident)a , John Turchiano MD (Instructor)b , Joseph D. Tobias MD (Vice-Chairman and Professor)a,b,⁎ a
Department of Pediatrics, University of Missouri, Columbia, MO, USA Department of Anesthesiology, University of Missouri, Columbia, MO 65212, USA
b
Received 30 January 2007; revised 28 June 2007; accepted 29 June 2007
Keywords: Intraoperative hypotension; Vasopressin infusion
Abstract A 56-year-old man, treated with an angiotensin II receptor antagonist for hypertension, presented for placement of a cochlear implant during general anesthesia. Intraoperatively, there was profound hypotension that was resistant to decreasing the anesthetic depth, fluid administration, as well as bolus doses of phenylephrine, ephedrine, and epinephrine. Hypotension was eventually successfully treated with a vasopressin infusion (0.06 U/min). Vasopressin may be a useful agent in such scenarios because its effect is not dependent on either adrenergic or angiotensin receptors, both of which may be affected by angiotensin II receptor antagonists. © 2008 Elsevier Inc. All rights reserved.
1. Introduction Hypotension during general anesthesia is generally easily treated by decreasing the depth of anesthesia and the administration of fluid. When needed, catecholamines, including phenylephrine, ephedrine, or epinephrine, are used due to their rapid onset and predictable hemodynamic response. Patients taking angiotensin-converting enzyme (ACE) inhibitors and angiotensin II receptor blocking agents preoperatively have a higher incidence of hypotension, more profound hypotension, and decreased responsiveness to exogenous catecholamines [1,2]. Although there
⁎ Corresponding author. Department of Anesthesiology; University of Missouri, Columbia, MO 65212, USA. Tel.: +1 573 882 7168; fax: +1 573 882 2226. E-mail address: [email protected] (J.D. Tobias). 0952-8180/$ – see front matter © 2008 Elsevier Inc. All rights reserved. doi:10.1016/j.jclinane.2007.06.023
are data to support the withholding of ACE inhibitors and angiotensin II receptor blocking agents on the morning of surgery so as to lessen the risk of hypotension [3,4], it is not a universally accepted practice. At our institution, patients taking these agents are generally instructed to take their usual morning dose. We present a patient who had recently been started on an angiotensin II receptor blocking agent, who experienced profound hypotension after induction of general anesthesia. The hypotension was refractory to conventional therapy including fluid administration and pharmacologic treatment with ephedrine, phenylephrine, and epinephrine. The case report emphasizes the potential for refractory hypotension associated with angiotensin II receptor blockers and discusses treatment with vasopressin agonists [1,2,5,6]. We also discuss potential mechanisms to explain the apparent catecholamine resistance in this patient population.
140
A.D. Wheeler et al.
2. Case report Review of this patient's hospital records and presentation of this case report were approved by the institutional review board of the University of Missouri, Columbia. The patient was a 56-year-old, 94-kg, 175-cm man, who presented for a cochlear implant for the treatment of hearing loss due to excessive noise exposure. His medical history was positive for hypertension, treated with hydrochlorothiazide 12.5 mg daily and irbesartan, an angiotensin II receptor blocker, 150 mg daily. There was no other history of heart disease. During his initial preoperative evaluation, his blood pressure (BP) was 168/107 mmHg, and he was referred back to his primary care physician (PCP) for better management of the hypertension. During the return visit to his PCP, his BP was 140/88 mmHg, and the irbesartan was increased to 300 mg daily because the patient did not tell the PCP that he had not been taking the 150-mg dose, which had been prescribed previously. This fact was not discovered until after the surgical procedure. On further investigation, it was learned that he had taken the 150-mg dose of irbesartan for only two days before the dose increase. He took the higher dose (300 mg) for 6 days before surgery. On the day of surgery, the
Table 1
patient was fasted (except for medications) for 6 hours. His BP was 145/98 mmHg in the preoperative holding area. He had taken the usual dose of both hydrochlorothiazide and irbesartan. A peripheral 18-gauge intravenous (IV) cannula was placed on the dorsum of the hand and midazolam 2 mg was administered. The patient was transported to the operating room (OR) where standard ASA monitors (temperature, noninvasive BP, 5-lead continuous electrocardiogram, end-tidal carbon dioxide, pulse oximetry, and precordial stethoscope) were placed. An IV fluid bolus of 500 mL of Ringer's lactate was administered, followed by induction of general anesthesia with fentanyl 50 μg, lidocaine 100 mg, propofol 250 mg, and succinylcholine 120 mg. Lidocaine was used because of the patient's history of hypertension in an attempt to blunt the response to intubation. Sevoflurane (inspired concentration 2%) was started before direct laryngoscopy and endotracheal intubation. Table 1 lists the subsequent hemodynamic parameters (heart rate and BP) and subsequent therapy. When ephedrine, phenylephrine, and epinephrine failed to increase BP, IV vasopressin (0.4 units) was administered. The dose was increased to 2 U every 10 minutes as it allowed for fewer doses, but BP remained labile, with systolic BP (SBP) ranging from 75 to 115 mmHg.
Intraoperative hemodynamic parameters and subsequent therapy
Time after intubation (min)
BP (mmHg)
Heart rate (bpm)
Treatment (IV)
−1 4
138/92 60/40
72 63
None Phn 100 μg, fluid bolus initiated, inhaled sevoflurane decreased from 2% to 0.5%
7 10 13 16
64/32 80/42 62/42 65/42
65 46 54 54
Phn 200 μg, Eph 10 mg Eph 20 mg, EPI 10 μg Eph 20 mg, EPI 20 μg, Phn 200 μg Eph 20 mg, EPI 20 μg, Phn 500 μg
19 21 24
120/54 70/48 90/54
46 65 75
45
75/38
55
90
83/35
64
Eph 20 mg, EPI 10 μg Phn 200 μg, ketamine 100 mg Phn 100 μg, ketamine 50 mg (two doses separated by 10 min) Phn 100 μg, Eph 20 mg, ketamine 50 mg (three doses separated by 10 min) Vasopressin 0.4 units
98 104 107 121
90/54 90/58 106/65 92/61
65 64 72 74
180 210
98/57 88/54
73 76
Vasopressin 0.4 units Vasopressin two units None Vasopressin two units every 15 min (5 doses) Vasopressin infusion at 0.04 U/min Vasopressin infusion increased to 0.06 U/min
Comment
Total 4 L of Ringer's lactate given during first 1.5 hrs. Radial pulses were faint but palpable. A different NIBP cuff was placed on right lower extremity, yielding similar results.
Patient coughing. BIS b 60 at this time and throughout case.
Surgical stimulation begins. Patient moving in response to surgical stimulation. BIS 50-56.
Propofol (50 μg/kg/min) and ketamine (3 mg/kg/hr) infusion started.
BP maintained without further intervention. Infusion stopped when patient awakened from general anesthesia.
Phn = phenylephrine; NIBP = noninvasive BP; Eph = ephedrine; EPI = epinephrine; BIS = bispectral index.
ARB and vasopressin To achieve steadier control of BP, a vasopressin infusion was started at 0.04 U/min and increased to 0.06 U/min, which maintained BP at 90 to 110/40 to 110/80 mmHg. Vasopressin was administered for a total of 165 minutes, with a continuous infusion given for 75 minutes. The entire case lasted 5 hours. Urine output during the case was 1.1 mL/kg/hr before vasopressin and 1.4 mL/kg/hr during vasopressin use. At the conclusion of the case, the propofol and ketamine infusions were discontinued and the vasopressin infusion was stopped when the patient awakened. The patient denied recall. There was no further hemodynamic instability. He was discharged home the following day and was doing well at a follow-up visit 1 week later.
3. Discussion Patients receiving medications that attenuate the reninangiotensin system in the preoperative period are known to have more frequent and more severe episodes of hypotension after induction of anesthesia [1,2]. After anesthetic induction, inhibition of the sympathetic nervous system by anesthetic agents results in alterations in cardiovascular function and BP that are usually attenuated by the angiotensin system [7]. Patients taking agents that antagonize this system are thus left without a key compensatory mechanism. Catecholamine resistance in patients taking ACE inhibitors and angiotensin II receptor blockers has been reported in the literature [8-10]. Eyraud et al [8] reported that 10 of 51 patients taking these agents had hypotension refractory to three doses of a catecholamine, and that these patients responded to the vasopressin agonist, terlipressin. In a cohort of adult patients undergoing cardiac surgery and cardiopulmonary bypass, Oh et al [9] reported that patients taking angiotensin II receptor blockers (candesartan, losartan, irbesartan, or valsartan) required higher doses of phenylepherine to maintain BP. Two animal studies provide some insight into a cellular mechanism that may explain the catecholamine-resistant hypotension noted in our patient. Godínez-Hernández et al [11] showed that rats treated with captopril had a decreased density of α1D-adrenergic receptors in the aorta. In addition, when phenylephrine was administered, there was a 60% decrease in the response of aortic contractility when compared with rats not treated with captopril. Godínez-Hu et al [12] showed that treatment of rat vascular smooth muscle cells with angiotensin II significantly increased the expression of α1D-adrenergic receptor messenger RNA when compared with cells not treated with angiotensin II. This effect was blocked by the administration of an angiotensin II receptor blocker. These studies suggest that vasopressin would be a logical alternative for the treatment of catecholamine-resistant hypotension because it depends neither on angiotensin nor the adrenergic receptors for its mechanism of action.
141 Vasopressin is a peptide hormone secreted by the hypothalamus in response to several stimuli, including decreased preload, increased plasma osmolarity, and decreased BP [12]. The primary functions of vasopressin include regulation of serum osmolarity and vascular tone. Vasopressin stimulates the V1 receptor, which is a G protein– coupled receptor, on vascular smooth muscle, thereby resulting in vasoconstriction. Use of the IV preparations (vasopressin, terlipressin) have been described for the treatment of hypotension in various clinical scenarios including hypotension refractory to catecholamines [5,6,13,14]. Terlipressin is also known as tricyl-lysinevasopressin. Its slow metabolism to the active lysinevasporessin provides for its longer half-life (6 hrs vs vasopressin's half-life of 6 min) [14]. Although most experience in the anesthesia literature has reported the use of terlipressin due to its longer half-life [1,2,8,13], this drug is not available at our institution. Therefore, we chose to use vasopressin, which is readily available in our ORs. Terlipressin has been well studied in patients with hypotension related to ACE inhibitors and angiotensin II receptor blockers. Meersschaert et al [15] randomized patients taking ACE inhibitors to receive ephedrine or terlipressin plus ephedrine for hypotension during general anesthesia. Patients receiving terlipressin in addition to ephedrine required less ephedrine (median dose of 3 vs 6 mg) to maintain normal BP. Boccara et al [16] randomized patients to receive terlipressin (intermittent 1 mg bolus doses) or a continuous infusion of norepinephrine in the treatment of ephedrine-resistant hypotension in patients receiving ACE inhibitors or angiotensin II receptor blockers during general anesthesia for carotid endarterectomy. Patients treated with terlipressin experienced a shorter duration of SBP measuring less than 90 mmHg. In addition, nonresponsiveness to therapy, defined as hypotension despite three boluses of terlipressin or three changes in the norepinephrine infusion rate, occurred in 0 of 10 patients treated with terlipressin versus 8 of 10 patients treated with norepinephrine. In our patient who failed to respond to multiple doses of various catecholamines, we noted a prompt response to the vasopressin bolus doses followed by maintenance of the BP with the vasopressin infusion. As previously mentioned, terlipressin is not available in our institution, although we would also postulate that in anesthetic practice, a continuous infusion of vasopressin may provide for more titratable control of BP than intermittent boluses of the longer-acting terlipressin. In addition, the anesthetic agent exacerbating hypotension is often quickly withdrawn at the conclusion of the case, which could result in rebound hypertension if terlipressin has been used. An important adverse effect of vasopressin agonists is the potential for hypoperfusion to “non-essential” tissues, with decreases in perfusion to the splanchnic and renal circulation [14,17], as the monitoring of urine output is important for ensuring adequate perfusion during the administration of vasopressin.
142 At the same time that we started vasopressin in our patient, we decreased the sevoflurane concentration and began IV anesthesia using a propofol-ketamine infusion. Although propofol likely results in greater myocardial depression than sevoflurane [18], in most patients, ketamine results in an increase in BP and cardiac output [19]. Ketamine was chosen to decrease the total dose of propofol and thereby limit propofol-related cardiovascular effects, including hypotension [20]. This combination was used in an attempt to achieve greater hemodynamic stability than sevoflurane alone and also ensure amnesia in a patient with hemodynamic instability. It is uncertain which role these agents played in the response to vasopressin. For the initial therapy for the hypotension, we chose to use intermittent doses of catecholamines rather than a continuous infusion because there was a minimal clinical response to the relatively high bolus doses of catecholamines including ephedrine, phenylephrine, and epinephrine. Given this lack of response, we did not think that there would be any advantage in using a continuous catecholamine infusion. In summary, patients receiving ACE inhibitors and angiotensin II receptor blockers can experience profound hypotension during general anesthesia. Although they are generally responsive to conventional therapy such as decreasing depth of anesthesia, administration of short-acting catecholamines, and fluids, refractory cases that necessitate additional therapy may occur. In such circumstances, vasopressin-receptor agonists may be effective. Given the potential for excessive vasoconstriction and decreases in endorgan perfusion, the dose of vasopressin should be titrated to maintain the lowest clinically acceptable BP level.
References [1] Brabant SM, Bertrand M, Eyraud D, Darmon PL, Coriat P. The hemodynamic effects of anesthetic induction in vascular surgical patients chronically treated with angiotensin II receptor antagonists. Anesth Analg 1999;89:1388-92. [2] Brabant SM, Eyraud D, Bertrand M, Coriat P. Refractory hypotension after induction of anesthesia in a patient chronically treated with angiotensin receptor antagonists. Anesth Analg 1999;89:887-8. [3] Comfere T, Sprung J, Kumar MM, et al. Angiotensin system inhibitors in a general surgical population. Anesth Analg 2005;100:636-44. [4] Bertrand M, Godet G, Meersschaert K, Brun L, Salcedo E, Coriat P. Should the angiotensin II antagonists be discontinued before surgery? Anesth Analg 2001;92:26-30.
A.D. Wheeler et al. [5] Jochberger S, Wenzel V, Dünser MW. Arginine vasopressin as a rescue vasopressor agent in the operating room. Curr Opin Anaesthesiol 2005;18:396-404. [6] Holmes CL, Patel BM, Russell JA, Walley KR. Physiology of vasopressin relevant to management of septic shock. Chest 2001; 120:989-1002. [7] Behnia R, Molteni A, Igic R. Angiotensin converting enzyme inhibitors: mechanisms of action and implications in anesthesia practice. Curr Pharm Des 2003;9:763-76. [8] Eyraud D, Brabant S, Nathalie D, et al. Treatment of intraoperative refractory hypotension with terlipressin in patients chronically treated with an antagonist of the renin-angiotensin system. Anesth Analg 1999;88:980-4. [9] Oh YJ, Lee JH, Nam SB, Shim JK, Song JH, Kwak YL. Effects of chronic angiotensin II receptor antagonist and angiotensin-converting enzyme inhibitor treatments on neurohormonal levels and haemodynamics during cardiopulmonary bypass. Br J Anaesth 2006;97:792-8. [10] Dendorfer A, Thornagel A, Raasch W, Grisk O, Tempel K, Dominiak P. Angiotenin II induces catecholamine release by direct ganglionic excitation. Hypertension 2002;40:348-54. [11] Godínez-Hernández D, Gallardo-Ortíz IA, López-Sánchez P, Villalobos-Molina R. Captopril therapy decreases both expression and function of alpha-adrenoceptors in pre-hypertensive rat aorta. Auton Autacoid Pharmacol 2006;26:21-9. [12] Hu ZW, Shi XY, Okazaki M, Hoffman BB. Angiotensin II induces transcription and expression of alpha 1-adrenergic receptors in vascular smooth muscle cells. Am J Physiol 1995;268(3 Pt 2): H1006-14. [13] Treschan TA, Peters J. The vasopressin system: physiology and clinical strategies. Anesthesiology 2006;105:599-612. [14] Delmas A, Leone M, Rousseau S, Albanese J, Martin C. Clinical review: vasopressin and terlipressin in septic shock patients. Crit Care 2005;9:212-22. [15] Meersschaert K, Brun L, Gourdin M, et al. Terlipressin-ephedrine versus ephedrine to treat hypotension at the induction of anesthesia in patients chronically treated with angiotensin converting-enzyme inhibitors: a prospective, randomized, double-blinded, crossover study. Anesth Analg 2002;94:835-40. [16] Boccara G, Ouattara A, Godet G, et al. Terlipressin versus norepinephrine to correct refractory arterial hypotension after general anesthesia in patients chronically treated with renin-angiotensin system inhibitors. Anesthesiology 2003;98:1338-44. [17] Dünser MW, Mayr AJ, Ulmer H, et al. Arginine vasopressin in advanced vasodilatory shock. A prospective, randomized, controlled study. Circulation 2003;107:2313-9. [18] De Hert SG, Cromheecke S, ten Broecke PW, et al. Effects of propofol, desflurane, and sevoflurane on recovery of myocardial function after coronary surgery in elderly high-risk patients. Anesthesiology 2003; 99:314-23. [19] Lippmann M, Appel PL, Mok MS, Shoemaker WC. Sequential cardiorespiratory patterns of anesthetic induction with ketamine in critically ill patients. Crit Care Med 1983;11:730-4. [20] Botero CA, Smith CE, Holbrook C, et al. Total intravenous anesthesia with a propofol-ketamine combination during coronary artery surgery. J Cardiothoracic Vasc Anesth 2000;14:409-15.