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

In patients chronically treated with angiotensin converting-enzyme inhibitors (ACEI), typically selected doses of ephedrine do not always restore arterial blood pressure when anesthesia-induced hypotension occurs. We postulated that the administration of terlipressin, an agonist of the vasopressin system, with ephedrine more effectively restores pressure in this setting than the administration of ephedrine alone. This prospective, randomized, cross-over, double-blinded study compared terlipressin combined with ephedrine (n = 19) with ephedrine alone (n = 21) in treating hypotension at the induction of anesthesia in 40 ACEI-treated patients undergoing hypotension (mean arterial blood pressure [MAP] <65 mm Hg or <30% of baseline value) after standardized anesthetic protocol (target-controlled IV anesthesia with propofol). Data are mean +/- SD. Patient characteristics, MAP, and heart rate before and after the induction of anesthesia during hypotensive episodes were not significantly different between the two groups. After the first bolus, MAP was significantly greater in the Terlipressin-Ephedrine group (72 +/- 12 mm Hg versus 65 +/- 8 mm Hg, P < 0.05). The occurrence of a second hypotensive episode (5% versus 71%, P < 0.001), the duration (2 +/- 1 min versus 3 +/- 1 min, P < 0.01) of hypotensive episodes, and the median dose of ephedrine (3 versus 6 mg, P < 0.05) were significantly less in the Terlipressin-Ephedrine group. In conclusion, terlipressin combined with ephedrine is more effective than ephedrine alone for treating anesthesia-induced hypotension in ACEI-treated patients. We conclude that this patient population with a partially blocked endogenous response to hypotension may be good candidates for successful use of a vasopressin analog to counteract intraoperative refractory hypotension. IMPLICATIONS: Vascular surgical patients chronically treated with drugs that inhibit the functioning of the renin-angiotensin system may experience hypotension unresponsive to conventional therapy. This double-blinded, cross-over study demonstrated that in these patients the use of a vasopressin analog, terlipressin given with ephedrine, was effective in reversing intraoperative systemic hypotension refractory to ephedrine.     

Prophylactic phenylephrine infusion for preventing hypotension during spinal anesthesia for cesarean delivery

In a randomized, double-blinded, controlled trial, we investigated the prophylactic infusion of IV phenylephrine for the prevention of hypotension during spinal anesthesia for cesarean delivery. Immediately after intrathecal injection, phenylephrine was infused at 100 microg/min (n = 26) for 3 min. From that point until delivery, phenylephrine was infused at 100 microg/min whenever systolic arterial blood pressure (SAP), measured each minute, was less than baseline. A control group (n = 24) received IV bolus phenylephrine 100 microg after each measurement of SAP <80% of baseline. Phenylephrine infusion decreased the incidence (6 [23%] of 26 versus 21 [88%] of 24; P < 0.0001), frequency, and magnitude (median minimum SAP, 106 mm Hg; interquartile range, 95-111 mm Hg; versus median, 80 mm Hg; range, 73-93 mm Hg; P < 0.0001) of hypotension compared with control. Heart rate was significantly slower over time in the infusion group compared with the control group (P < 0.0001). Despite a large total dose of phenylephrine administered to the infusion group compared with the control group (median, 1260 microg; interquartile range, 1010-1640 microg; versus median, 450 microg; interquartile range, 300-750 microg; P < 0.0001), umbilical cord blood gases and Apgar scores were similar. One patient in each group had umbilical arterial pH <7.2. Prophylactic phenylephrine infusion is a simple, safe, and effective method of maintaining arterial blood pressure during spinal anesthesia for cesarean delivery. IMPLICATIONS: In patients receiving spinal anesthesia for elective cesarean delivery, a prophylactic infusion of phenylephrine 100 microg/min decreased the incidence, frequency, and magnitude of hypotension with equivalent neonatal outcome compared with a control group receiving IV bolus phenylephrine.     

The effects of clonidine on sensitivity to phenylephrine and nitroprusside in patients with essential hypertension recovering from surgery

Clonidine reduces postoperative circulatory instability in patients with essential hypertension. It also increases the sensitivity to vasopressors before and during anesthesia. We investigated blood pressure responses to phenylephrine and nitroprusside pre- vs postoperatively and the effect of clonidine on these responses in patients with essential hypertension. Twenty patients received clonidine 6 microg/kg orally 120 min before anesthesia and 3 microg/kg IV over the final hour of surgery or an identical placebo. During increasing bolus doses of phenylephrine and nitroprusside (30-300 microg), the maximal systolic pressure responses were recorded at baseline on the day before surgery, before the induction of anesthesia, and 1 and 3 h postoperatively. Sensitivity to phenylephrine and nitroprusside was interpolated from linear regression of the data. There was no difference between preoperative and postoperative sensitivity to phenylephrine or nitroprusside in either group. Clonidine increased sensitivity to phenylephrine versus placebo before and after surgery (response to dose of 1.5 microg/kg: 42+/-14 vs 27+/-8 mm Hg preinduction, 37+/-10 vs 26+/-8 mm Hg 3 h postoperatively; both P < 0.01), but not to nitroprusside (38+/-6 vs 37+/-10 mm Hg preinduction and 40+/-6 vs 39+/-8 mm Hg postoperatively). Clonidine increases the sensitivity to phenylephrine but not nitroprusside at baseline and postoperatively in hypertensive patients. IMPLICATIONS: Clonidine increases the sensitivity to bolus injections of the vasoconstrictor phenylephrine, but not the vasodilator sodium nitroprusside, before and after surgery in patients with preexisting hypertension. The doses of vasopressors should be reduced accordingly in hypertensive patients receiving perioperative clonidine.     

Prevention of spinal anaesthesia-induced hypotension in the elderly: i.m. methoxamine or combined hetastarch and crystalloid

We have compared two methods of reducing hypotension during spinal anaesthesia in elderly patients, 6% hetastarch and crystalloid or methoxamine 10 mg i.m., in terms of haemodynamic stability and requirements for additional vasopressors. Sixty-two patients (aged 60- 97 yr) undergoing surgical fixation of fractured neck of femur were allocated randomly to receive 6% hetastarch (Hespan) 500 ml followed by Hartmann's solution 500 ml (group HS, n = 32) or a bolus injection of methoxamine 10 mg i.m. (group MX, n = 30), 10 min before induction of spinal anaesthesia with 0.5% hyperbaric bupivacaine 2.25-3.0 ml. Arterial pressure was measured non-invasively by an oscillotonometer at 2-min intervals from 0 to 40 min and at 5-min intervals thereafter. Methoxamine 2 mg i.v. was given if systolic arterial pressure (SAP) decreased to < 100 mm Hg. Hypotension was defined as a 25% decrease from baseline SAP or mean arterial pressure (MAP). Patient data, sensory level and blood loss were similar in the two groups. SAP and MAP increased initially from baseline until induction of spinal anaesthesia and then decreased for 30 min in both groups, but remained higher in group MX (P < 0.05). Heart rate (HR) decreased from baseline in group MX (P < 0.05) and was less than in group HS at all times from 2 to 60 min (P < 0.01). The incidence of SAP hypotension (47% vs 75%; P = 0.03, odds ratio (OR) = 3.43) and MAP hypotension (47% vs 67%; P = 0.09, OR = 2.51) was less in group MX than in group HS. Requirements for rescue methoxamine i.v. (27% vs 53%, P = 0.04, OR = 3.11) was less in group MX than in group HS but the dose of rescue methoxamine given (mean 6.3 (95% confidence intervals 3.0-9.6) vs 8.9 (5.6-12.2) mg) and time to onset of hypotension (20.7 (14.5-26.7) vs 17.3 (11.4-23.1) min) were similar in groups MX and HS, respectively. We conclude that methoxamine 10 mg i.m., given 10 min before induction of spinal anaesthesia in normovolaemic elderly patients, reduced subsequent SAP and MAP hypotension, HR and requirements for rescue vasopressor therapy compared with a combination of 6% hetastarch 500 ml and crystalloid 500 ml. The previously reported benefit of such volume administration may not extend to the elderly.      

Phenylephrine added to prophylactic ephedrine infusion during spinal anesthesia for elective cesarean section

BACKGROUND: Because ephedrine infusion (2 mg/min) does not adequately prevent spinal hypotension during cesarean delivery, the authors investigated whether adding phenylephrine would improve its efficacy. METHODS: Thirty-nine parturients with American Society of Anesthesiologists physical status I-II who were scheduled for cesarean delivery received a crystalloid preload of 15 ml/kg. Spinal anesthesia was performed using 11 mg hyperbaric bupivacaine, 2.5 microg sufentanil, and 0.1 mg morphine. Maternal heart rate and systolic blood pressure were measured at frequent intervals. A vasopressor infusion was started immediately after spinal injection of either 2 mg/min ephedrine plus 10 microg/min phenylephrine or 2 mg/min ephedrine alone. Treatments were assigned randomly in a double-blind fashion. The infusion rate was adjusted according to systolic blood pressure using a predefined algorithm. Hypotension, defined as systolic blood pressure less than 100 mmHg and less than 80% of baseline, was treated with 6 mg ephedrine bolus doses. RESULTS: Hypotension occurred less frequently in the ephedrine-phenylephrine group than in the ephedrine-alone group: 37% versus 75% (P = 0.02). Ephedrine (36+/-16 mg, mean +/- SD) plus 178+/-81 microg phenylephrine was infused in former group, whereas 54+/-18 mg ephedrine was infused in the latter. Median supplemental ephedrine requirements and nausea scores (0-3) were less in the ephedrine-phenylephrine group (0 vs. 12 mg, P = 0.02; and 0 vs. 1.5, P = 0.01, respectively). Umbilical artery pH values were significantly higher in the ephedrine-phenylephrine group than in the group that received ephedrine alone (7.24 vs. 7.19). Apgar scores were similarly good in both groups. CONCLUSION: Phenylephrine added to an infusion of ephedrine halved the incidence of hypotension and increased umbilical cord pH.     

An open-label randomized controlled clinical trial for comparison of continuous phenylephrine versus norepinephrine infusion in prevention of spinal hypotension during cesarean delivery

BackgroundDuring spinal anesthesia for cesarean delivery phenylephrine is the vasopressor of choice but can cause bradycardia. Norepinephrine has both β- and α-adrenergic activity suitable for maintaining blood pressure with less bradycardia. We hypothesized that norepinephrine would be superior to phenylephrine, requiring fewer rescue bolus interventions to maintain blood pressure.MethodsEighty-five parturients having spinal anesthesia for elective cesarean delivery were randomized to Group P (phenylephrine 0.1 μg/kg/min) or Group N (norepinephrine 0.05 μg/kg/min) fixed-rate infusions. Rescue bolus interventions of phenylephrine 100 μg for hypotension, or ephedrine 5 mg for bradycardia with hypotension, were given as required to maintain systolic blood pressure. Maternal hemodynamic variables were measured non-invasively.ResultsThere was no difference between groups in the proportion of patients who required rescue vasopressor boluses (Group P: 65.8% [n=25] vs. Group N: 48.8% [n=21], P=0.12). The proportion of patients who received ⩾1 bolus of phenylephrine was similar between groups (Group P: 52.6% [n=20] vs. Group N: 46.5% [n=20], P=0.58). However, more patients received ⩾1 bolus of ephedrine in the phenylephrine group (Group P: 23.7% [n=9] vs. Group N: 2.3% [n=1], P <0.01). The incidence of emesis was greater in the phenylephrine group (Group P: 26.3% vs. Group P: 16.3%, P <0.001). Hemodynamic parameters including heart rate, the incidence of bradycardia, blood pressure, cardiac output, cardiac index, stroke volume, and systemic vascular resistance and neonatal outcome were similar between groups (all P <0.05).ConclusionNorepinephrine fixed-rate infusion has efficacy for preventing hypotension and can be considered as an alternative to phenylephrine.     

Effects of isoflurane, midazolam, and etomidate on cardiovascular responses to stimulation of central nervous system pressor sites in chronically instrumented cats.

The systemic hemodynamic actions of isoflurane (a volatile anesthetic) and etomidate and midazolam (intravenous anesthetics) have been well documented. However, few studies have investigated the actions of these agents on central cardiovascular control sites. The present investigation examined the actions of these agents on the responses of systolic arterial pressure (SAP), heart rate, infrarenal aortic blood flow, and lower body vascular resistance to central nervous system pressor site stimulation in chronically instrumented cats. Male and female cats (n = 23) were chronically instrumented with bipolar stimulating electrodes in the regions of the ventrolateral hypothalamus (anterior, 10.0 mm; lateral, 2.5 mm; depth, -4.0 mm) and mesencephalic reticular formation (anterior, 2.0 mm; lateral, 2.0 mm; depth, -1.0 mm). Control experiments consisted of stimulation sequences at 1x, 2x, and 4x threshold current levels to elicit pressor responses. Stimulation of the hypothalamic site produced current-dependent increases in SAP (6-85 mm Hg), in heart rate (3-56 beats/min), and in infrarenal aortic blood flow (0-85 mL/min). Reticular formation site stimulation produced graded increases in SAP (6-129 mm Hg) only. Isoflurane (1.5%, 2.5%, and 3.0%), etomidate (3.0-mg/kg bolus and 0.4-mg.kg-1. h-1 infusion), and midazolam (7.5-mg/kg bolus and 0.2-mg.kg-1.h-1 infusion) were then administered in separate experimental groups. After a steady hemodynamic state was established with each agent, stimulation sequences were repeated. Isoflurane produced an attenuation of the responses of SAP (from 85.1 +/- 8.2 to 17.8 +/- 6.1 mm Hg at 1.5%, to 7.2 +/- 2.0 mm Hg at 2.5%, and to 4.7 +/- 2.0 mm Hg at 3%, all P less than 0.05), heart rate (from 41.1 +/- 13.0 to 12.5 +/- 2.7 beats/min at 2.5% and to 6.2 +/- 1.7 beats/min at 3%, all P less than 0.05), and of the infrarenal aortic blood flow (from 72.6 +/- 14.3 to 11.8 +/- 4.2 mL/min at 1.5%, to 10.2 +/- 5.6 mL/min at 2.5%, and to 3.2 +/- 1.5 mL/min at 3%, all P less than 0.05) to the highest level of hypothalamic site stimulation. Isoflurane similarly produced an attenuation of the SAP response (from 128.7 +/- 10.3 to 15.4 +/- 8.1 mm Hg at 1.5%, to 0.2 +/- 1.1 mm Hg at 2.5%, and to 0.3 +/- 0.5 mm Hg at 3.0%, all P less than 0.05) to the highest level of reticular formation site stimulation.(ABSTRACT TRUNCATED AT 400 WORDS)     

Phenylephrine Added to Prophylactic Ephedrine Infusion during Spinal Anesthesia for Elective Cesarean Section

Background: Because ephedrine infusion (2 mg/min) does not adequately prevent spinal hypotension during cesarean delivery, the authors investigated whether adding phenylephrine would improve its efficacy.

Methods: Thirty-nine parturients with American Society of Anesthesiologists physical status I-II who were scheduled for cesarean delivery received a crystalloid preload of 15 ml/kg. Spinal anesthesia was performed using 11 mg hyperbaric bupivacaine, 2.5 [mu]g sufentanil, and 0.1 mg morphine. Maternal heart rate and systolic blood pressure were measured at frequent intervals. A vasopressor infusion was started immediately after spinal injection of either 2 mg/min ephedrine plus 10 [mu]g/min phenylephrine or 2 mg/min ephedrine alone. Treatments were assigned randomly in a double-blind fashion. The infusion rate was adjusted according to systolic blood pressure using a predefined algorithm. Hypotension, defined as systolic blood pressure less than 100 mmHg and less than 80% of baseline, was treated with 6 mg ephedrine bolus doses.

Results: Hypotension occurred less frequently in the ephedrine-phenylephrine group than in the ephedrine-alone group: 37%versus 75% (P = 0.02). Ephedrine (36 +/-16 mg, mean +/- SD) plus 178 +/-81 [mu]g phenylephrine was infused in former group, whereas 54 +/-18 mg ephedrine was infused in the latter. Median supplemental ephedrine requirements and nausea scores (0-3) were less in the ephedrine-phenylephrine group (0 vs. 12 mg, P = 0.02; and 0 vs. 1.5, P = 0.01, respectively). Umbilical artery p H values were significantly higher in the ephedrine-phenylephrine group than in the group that received ephedrine alone (7.24 vs. 7.19). Apgar scores were similarly good in both groups.     

Cardiodynamic effects of propofol in comparison with thiopental: assessment with a transesophageal echocardiographic approach

In 40 patients, the cardiovascular effects of low- and high-dose propofol anesthesia (single bolus of 1.5 mg/kg in group A, 2.5 mg/kg in group C) were examined and compared with those of low- and high-dose thiopental (4 mg/kg in group B, 6.5 mg/kg in group D) (n = 10 patients per group). After induction of anesthesia with etomidate, all patients were ventilated with 70% nitrous oxide in oxygen. Peripheral arterial systolic blood pressure (SAP) and transesophageal echocardiographic short-axis measurements were used to calculate the end-systolic pressure-volume relationship (E) as an index of global myocardial contractility. In all groups SAP decreased significantly below baseline levels for the duration of the measurements (15 min after drug administration), except for the lower dose of thiopental, where SAP returned to baseline values within 10 min. Propofol at a dose of 1.5 mg/kg significantly decreased cardiac output (CO) (from 5.1 +/- 0.25 [mean +/- SEM] to 4.2 +/- 0.23 L/min), stroke volume (SV) (from 64 +/- 3 to 56 +/- 3.6 mL), and the slope of E (from 71 +/- 3.5 to 65 +/- 4.2 mm Hg/mL) until 4 min after drug administration. The higher dose of propofol significantly decreased CO (from 5.1 +/- 0.29 to 4.1 +/- 0.26 L/min), SV (from 64 +/- 3 to 52 +/- 4.6 mL), and the slope of E (from 71 +/- 3.6 to 62 +/- 3.7 mm Hg/mL) until 10 min after drug administration.(ABSTRACT TRUNCATED AT 250 WORDS)     

Regional anesthesia for carotid surgery: less intraoperative hypotension and vasopressor requirement

Regional anesthesia (RA) is the gold standard of neuromonitoring during carotid endarterectomy (CEA). Recent data show that RA for CEA is associated with fewer postoperative complications. The aim of the present study was to assess hemodynamic stability and vasoactive drug use for CEA performed under RA versus general anesthesia (GA). All patients undergoing CEA from January 2005 to January 2006 were identified from our prospective database. Electronic and paper charts were reviewed. Intraoperative monitoring data were reviewed retrospectively. Hypotension was defined as systolic blood pressure (SBP) <100 mm Hg and deemed prolonged if it lasted more than 10 min. Hypertension was defined as SBP >160 mm Hg. BP variation was defined as the difference between the highest and lowest SBP, and bradycardia as heart rate (HR) below 60. The data were expressed as means +/- standard deviation. Seventy-two consecutive patients underwent CEA: 25 under RA and 47 under GA. There was no difference in preoperative HR and BP. Most patients had symptomatic severe carotid stenosis (80% in RA vs. 85% in GA, nonsignificant). Intraoperatively, RA was associated with less BP variation (60 +/- 27 vs. 78 +/- 22 mm Hg, p = 0.005), bradycardia (5% vs. 63%, p < 0.001), hypotension (20% vs. 70%, p < 0.01), and prolonged hypotension (0% vs. 23%, p = 0.009) and more hypertension (80% vs. 47%, p = 0.007). Vasopressor requirements were less frequent under RA (20% vs. 77%, p < 0.001). There was no significant difference between groups in hypotension or hypertension episodes seen in the postoperative recovery room. RA was associated with less hypotension and less vasopressor used during CEA compared to GA. The improved hemodynamic stability may account for the lower incidence of complications after CEA.     

Terlipressin versus norepinephrine to counteract anesthesia-induced hypotension in patients treated with renin-angiotensin system inhibitors: effects on systemic and regional hemodynamics

BACKGROUND: Terlipressin has been suggested as the ideal drug to treat anesthesia-induced hypotension in patients under long-term renin-angiotensin system inhibitor treatment for arterial hypertension. The authors compared the effects of terlipressin and norepinephrine on systemic hemodynamic parameters and gastric mucosal perfusion using a laser Doppler flowmetry technique in patients treated with renin-angiotensin system inhibitors who experienced hypotension at induction of anesthesia. METHODS: Thirty-two patients scheduled for carotid endarterectomy under general anesthesia and treated with renin-angiotensin system inhibitors had hypotension after induction of general anesthesia. They were randomized to receive 1 mg of terlipressin (n = 16) or norepinephrine infusion (n = 16) to counteract anesthesia-induced hypotension. A laser Doppler probe was introduced into the gastric lumen. All measurements were performed just before surgery, during hypotension, at 30 min, and at 4 h. RESULTS: Terlipressin produced an increase in mean arterial pressure and a decrease in gastric mucosal perfusion detected by laser Doppler flowmetry (P < 0.05) over 30 min that were sustained for 4 h. During the infusion, norepinephrine produced an increase in mean arterial pressure and in gastric mucosal perfusion detected by laser Doppler flowmetry (P < 0.05). If compared to norepinephrine, terlipressin reduced oxygen delivery and oxygen consumption (P < 0.05) and increased arterial lactate concentrations (P < 0.05). CONCLUSION: This study showed the efficacy of terlipressin in the treatment of hypotension episodes in anesthetized patients chronically treated with renin-angiotensin system inhibitors, angiotensin converting-enzyme inhibitors, and angiotensin II receptor antagonists. However, the negative effects on gastric mucosal perfusion and the risk of iatrogenic oxygen supply dependency of terlipressin need to be taken into account.     

Left stellate ganglion block has only small effects on left ventricular function in awake dogs before and after induction of heart failure

Left stellate ganglion block (LSGB) results in acute sympathetic denervation of the left ventricular (LV) posterobasal wall. We investigated the effects of LSGB in chronically instrumented awake dogs before and after the induction of pacing-induced congestive heart failure. Twelve dogs were instrumented for measurement of global hemodynamics [LV pressure (LVP)], its first derivative (dP/dt), cardiac output (CO), and regional myocardial function (systolic posterobasal segment length shortening, mean velocity [SLmv]). Before the induction of heart failure (n = 12), LSGB did not affect CO [3.2+/-1.4 (control, mean +/- SD) vs. 3.3+/-1.6 L/min (LSGB, P = 0.45)] and SLmv (11.1+/-4.0 vs. 10.8+/-4.0 mm/s, P = 0.16), but slightly reduced LVP (130+/-12 vs. 125+/-14 mm Hg, P = 0.04), dP/dt(max) (3614+/-755 vs. 3259+/-644 mm Hg/s, P = 0.003) and dP/dt(min) (-3153+/-663 vs. -2970+/-725 mm Hg/s, P = 0.03). During heart failure (n = 8), global hemodynamics [CO (2.8+/-1.2 vs. 2.7+/-1.2 L/min, P = 0.04), LVP (119+/-6 vs. 112+/-9 mm Hg, P = 0.01), dP/dt(max) (1945+/-520 vs. 1824+/-554 mm Hg/s, P = 0.03) and dP/dt(min) (-2402+/-678 vs. -2243+/-683 mm Hg/s, P = 0.04)], as well as regional myocardial function, were significantly different after LSGB [SLmv] (8.0+/-3.8 vs. 6.9+/-3.4 mm/s, P = 0.02)]. In conclusion, even during heart failure, the hemodynamic changes after LSGB are small, confirming its broad margin of safety.     

Should the angiotensin II antagonists be discontinued before surgery?

Angiotensin II antagonists (AIIA) are part of a new rational treatment of hypertension. Because adverse circulatory effects during anesthesia can occur in patients chronically treated with angiotensin-converting enzyme inhibitors, some clinicians discontinue them at least 24 h before operation. No data are available concerning AIIA administration in patients scheduled for vascular surgery performed under general anesthesia. The aim of this prospective randomized study was to compare hemodynamics during induction of anesthesia in patients chronically treated with AIIA and those of patients not receiving this drug on the morning before operation. Thirty-seven patients chronically treated with AIIA for hypertension were randomly assigned to two groups: Group I: AIIA discontinued on the day before surgery (n = 18); Group II: AIIA given 1 h before anesthesia (n = 19). Patients received sufentanil 0.4 microg/kg, propofol 1.5 mg/kg, and atracurium 0.5 mg/kg. During the procedure, the anesthesiologist was required to maintain systolic blood pressure and heart rate within 30% of baseline values using intravascular fluid administration and vasoconstric- tors (e.g. , ephedrine, phenylephrine, or terlipressin). Hemodynamic variables were recorded each 1 min. Hemodynamic study ended at incision. The number and duration of hemodynamic events were collected, and total doses of vasoactive drugs were noted in each group. Systolic arterial pressure was significantly decreased in Group II at 5, 15 and 23 min after induction of anesthesia (*P < 0.05). In this group, the decrease in systolic arterial pressure was associated with more frequent episodes of hypotension (AIIA withdrawn: 1 +/- 1; AIIA given: 2 +/- 1; P < 0.01), with a larger number of patients developing at least 1 episode of hypotension (AIIA withdrawn: 12; AIIA given: 19; P < 0.01), and a longer duration of an episode of hypotension (AIIA withdrawn: 3 +/- 4 min; AIIA given: 8 +/- 7 min; P < 0.01), and an increased need for vasoactive drugs. In conclusion, blockade of the renin-angiotensin system increases the potential hypotensive effect of anesthetic induction. A severe hypotensive episode, requiring vasoconstrictor treatment, occurs after induction of general anesthesia in patients chronically treated with AIIA. Recommendations to discontinue AIIA drugs on the day before the surgery may be justified. Implications: This prospective randomized study demonstrated that more severe hypotensive episodes, requiring vasoconstrictor treatment, occur after induction of general anesthesia in patients chronically treated with AIIA and receiving this drug on the morning before operation, in comparison with those in whom AIIA were discontinued on the day before operation. Recommendations to discontinue these drugs on the day before the surgery may be justified.     

beta2-adrenoceptor genotype affects vasopressor requirements during spinal anesthesia for cesarean delivery

BACKGROUND: Maternal hypotension is common after spinal anesthesia for cesarean delivery. There is wide variability in the incidence and severity of hypotension and in the response to treatment. The beta2 adrenoceptor (beta2AR) possesses several polymorphic sites. Codons 16 (Arg16Gly) and 27 (Glu27Gln) have been shown to affect desensitization of the receptor. The goal of this study was to determine whether genetic variants of the beta2AR alter incidence of hypotension or the amount of vasopressor treatment required during spinal anesthesia for cesarean delivery. METHODS: One hundred seventy healthy women undergoing elective cesarean delivery were studied. Spinal anesthesia was performed with 12 mg hyperbaric bupivacaine, 25 microg fentanyl, and 200 microg morphine. Hypotension was treated with ephedrine and/or phenylephrine intravenously, and beta2AR genotype at codons 16 and 27 was determined. Analysis of variance was used to compare variables between genotypes, with data expressed as mean +/- SD. RESULTS: Ephedrine or phenylephrine was used in more than 90% of patients, with no difference in the incidence of hypotension between beta2AR genotypes. However, there was a significant effect of genotype on the amount of vasopressor required. Gly16 homozygotes received significantly less ephedrine (18 +/- 14 mg) than Arg16 homozygotes (28 +/- 13 mg) and Arg16Gly heterozygotes (30 +/- 20 mg; P = 0.0005). Glu27 homozygotes required significantly less ephedrine than Gln 27 homozygotes (14 +/- 13 vs. 30 +/- 19 mg; P = 0.002). Gln27Glu heterozygotes received less ephedrine than Gln27 homozygotes (23 +/- 16 vs. 30 +/- 19 mg; P = 0.03). CONCLUSIONS: Glycine at position 16 and/or glutamate at position 27 of the beta2AR leads to lower vasopressor use for treatment of hypotension during spinal anesthesia.     

Potential renal protective benefits of intra-operative BNP infusion during cardiac transplantation

BACKGROUND: Recombinant BNP (nesiritide) is known to reduce endothelin levels, cause afferent arteriole vasodilation, and increase natriuresis and diuresis. We hypothesized that intraoperative infusion of BNP may benefit renal function in cardiac transplant patients. METHODS: From June 2003 to September 2005, 22 consecutive heart transplant patients received BNP at a dose of 0.01 microg/kg/min before initiation of cardiopulmonary bypass (group A). BNP infusion was continued for a mean of 3.3 +/- 1.9 days. Hemodynamics, urine output, and serum creatinine levels were prospectively collected and compared with 22 consecutive patients who underwent heart transplantation between May 2002 and June 2003 following the identical transplant protocol, but without BNP infusion (group B). RESULTS: At 24 hours postoperatively, mean blood pressure was comparable between groups (87 +/- 11 mm Hg vs 89 +/- 17 mm Hg, P = .7), but pulmonary artery pressure (18 +/- 5 mm Hg vs 24 +/- 5 mm Hg, P = .001) and central venous pressure (12 +/- 5 mm Hg vs 16 +/- 4 mm Hg, P = .01) were lower with BNP infusion, whereas cardiac index was augmented (2.8 +/- 0.5 vs 2.4 +/- 0.6, P = .03). Requirement of low-dose inotropic and vasopressor support was equally distributed between groups (P > or = .72). Postoperative urine output for the initial 24 hours was higher in group A (84 +/- 15 vs 55 +/- 36 mL/h, P = .01). None of the patients with BNP infusion required additional diuretics or renal replacement therapy during the first week after transplantation. Mean postoperative serum creatinine levels as compared with preoperative values remained unchanged within group A (P = .12), but increased significantly in group B (P < .001). CONCLUSIONS: Intraoperative BNP infusion in heart transplant recipients was associated with favorable postoperative hemodynamics, significantly improved urine output, and stable serum creatinine levels. A prospective, randomized, multicenter trial is warranted to evaluate the potential renal protective benefits of intraoperative BNP infusion in this patient population.     

Analysis of parameters associated with hypotension requiring vasopressor support after carotid angioplasty and stenting

INTRODUCTION: Systemic hypotension has been observed for up to 36 hours in response to stimulation of the carotid baroreceptor by carotid angioplasty and stenting (CAS). The aim of this study was to identify risk factors and cardiac outcomes for postprocedural hypotension requiring vasopressor support after CAS. METHODS: Between 2003 and 2005, 143 patients (87 men; mean age, 75 years) with high-grade carotid artery stenosis (mean, 87.3%) were treated with CAS and prospectively entered into a vascular registry. Data were retrospectively analyzed to determine factors predictive of hypotension requiring vasopressor support after CAS. Atropine and appropriate intravenous crystalloid solution were administered during CAS. For the first 30 patients, atropine was only used for symptomatic patients but then became routine and was used for all patients with primary carotid stenosis. Hypotension (systolic blood pressure <90 mm Hg or a mean arterial blood pressure <50 mm Hg) unresponsive to conservative measures was treated with vasopressors (phenylephrine or norepinephrine). Patients were stratified into three groups based on hypotension requiring vasopressors: (1) no vasopressors, (2) vasopressors for < or = 24 hours (short duration), and (3) vasopressors for >24 hours (prolonged duration). Risk factors for hypotension requiring vasopressors were analyzed by univariate and multivariate logistic regression analysis. RESULTS: Postprocedural hypotension requiring vasopressor treatment was seen in 16 (11%) of 143 of patients, with 6 (4%) requiring vasopressor support for >24 hours. Mean duration of vasopressor administration for all patients was 17 +/- 10 hours (range, 6 to 36 hours). By univariate analysis, a history of a previous myocardial infarction (P = .02) or use of the PercuSurge occlusion balloon (P = .05) were both associated with increased incidence of short duration (80 years old (P = .02) were associated with prolonged (>24 hours) vasopressor requirement. On multivariate analysis adjusted for age and sex, a history of myocardial infarction (odds ratio [OR], 4.1; 95% confidence interval [CI], 1.0 to 16.4; P = .05) remained an independent predictor of short-duration vasopressors. On multivariate analysis, female sex (OR, 10.9; 95% CI, 1.2 to 100.4; P = .04) and age >80 years old (OR, 13.8, 95% CI, 1.5 to 127.2; P = .02) remained independent predictors of prolonged vasopressor use. The incidence of periprocedural myocardial infarctions, arrhythmias, or congestive heart failure did not differ between those patients who did not receive vasopressors (5/127) and those who received vasopressors for a short (< or = 24 hours) duration (1/10, P = NS) or prolonged (>24 hours) duration (0/6, P = NS). CONCLUSION: Prolonged hypotension requiring vasopressor support occurs in a minority of patients after CAS, with higher incidences in older women. In contrast, hypotension requiring a more limited duration of vasopressor use occurs more commonly in patients who had a prior myocardial infarction, independent of age or sex. In this cohort of patients, vasopressors required for hypotension were not associated with an increased incidence of periprocedural cardiac complications. Despite the increased incidence of prolonged hypotension in older women, this study demonstrates that CAS can be performed without an increase in cardiac morbidity in older women.     

Hypotension and hypertension as consequences of baroreceptor dysfunction following carotid endarterectomy.

Arterial pressure regulation is often labile following carotid endarterectomy. Hemodynamic data from 100 consecutive endarterectomies allowed definition of three distinct postoperative blood pressure responses. A hypotensive response (group I) affected 28 patients in whom mean arterial pressure decreased from 168 +/- 29/90 +/- 15 mm Hg before operation to 110 +/- 21/68 +/- 16 mm Hg after operation (P less than 0.001). Maximum hypotension occurred 5.3 hours after endarterectomy. The preoperative pulse, 80 +/- 9 beats/min, fell to a low of 64 +/- 12 beats/min after operation (P less than 0.001). A significant hypertensive response (group II) affected 19 patients in whom mean blood pressure rose from 160 +/- 29/87 +/- 15 to 223 +/- 32/110 +/- 22 mm Hg (P less than 0.001). Maximum hypertension was noted 2.3 hours after endarterectomy. This was unaccompanied by significant pulse changes. Fifty-three patients remained normotensive (group III). Their preoperative blood pressure (150 +/- 14 mmHg). Fluctuations in pressure did not correlate with age, indication for operation, or degree of ipsilateral and contralateral carotid arterial stenosis. Postendarterectomy hypotension and hypertension appear to represent transient baroreceptor dysfunctions.     

Hemodynamic effects of spinal anesthesia and simultaneous intravenous bolus of combined phenylephrine and ephedrine versus ephedrine for cesarean delivery

BACKGROUND: Hypotension following spinal anesthesia for cesarean delivery can produce adverse maternal symptoms and neonatal acid-base effects. Single-agent prophylaxis, most notably with ephedrine, does not reliably prevent spinal anesthesia-induced hypotension; recently, however, the prophylactic use of phenylephrine with ephedrine as an infusion was observed to be effective. We postulated that this combination, when given as an intravenous bolus for prophylaxis and rescue treatment, could be similarly effective. METHOD: Forty-three term parturients were randomized to receive a bolus of ephedrine 10 mg +/- phenylephrine 40 microg (groups E and EP, respectively) simultaneously with spinal anesthesia. Hypotension was defined as a systolic blood pressure below 100 mmHg or a decrease of 20% from a baseline value. Rescue boluses comprised of ephedrine 5 mg +/- phenylephrine 20 microg. RESULTS: For groups E and EP, respectively, the incidence of hypotension was 80% vs. 95% (P=0.339), with the mean number of rescue boluses being 3.85+/-3.7 and 3.05+/-1.7 and the mean umbilical artery pH being 7.246+/-0.081 vs. 7.244+/-0.106. All comparisons were not significant (NS). CONCLUSION: The combination of ephedrine and phenylephrine given as an intravenous bolus at the doses selected is not superior to ephedrine alone in preventing or treating hypotension in healthy parturients undergoing cesarean delivery.     

Use of esmolol during anesthesia to treat tachycardia and hypertension

We evaluated the clinical effectiveness of esmolol, an ultra-short-acting, cardioselective beta-adrenergic receptor blocker, in controlling sinus tachycardia and increased systolic blood pressure occurring perioperatively in 30 ASA physical status II or III patients having elective, non-cardiac surgery. Esmolol 80 mg I.V. bolus (N = 15) or placebo (N = 15) followed by 12 mg/min or placebo were infused in 30 isoflurane-anesthetized patients using a randomized double-blind study design. The bolus plus infusions were given when surgical stimuli caused heart rate to exceed 95 bpm or systolic blood pressure 140 mm Hg. Esmolol significantly decreased heart rate (107 +/- 4, mean +/- SEM to 99 +/- 4, mean +/- SEM bpm) within 45 sec after starting the bolus plus infusion; the placebo had no effect, heart rate being 105 +/- 4 before and 106 +/- 3 bpm after the bolus plus infusion. Patients given esmolol continued to have heart rates significantly lower than patients given placebo injections throughout a six min infusion (Ex., at 5 min 81 +/- 3 vs 91 +/- 4 bpm). The study demonstrated no apparent effect of esmolol on blood pressure but that esmolol is effective in treating perioperative sinus tachycardia.     

Ethyl pyruvate preserves cardiac function and attenuates oxidative injury after prolonged myocardial ischemia

OBJECTIVE: Myocardial injury and dysfunction following ischemia are mediated in part by reactive oxygen species. Pyruvate, a key glycolytic intermediary, is an effective free radical scavenger but unfortunately is limited by aqueous instability. The ester derivative, ethyl pyruvate, is stable in solution and should function as an antioxidant and energy precursor. This study sought to evaluate ethyl pyruvate as a myocardial protective agent in a rat model of ischemia-reperfusion injury. METHODS: Rats underwent 30-minute ischemia and 30-minute reperfusion of the left anterior descending coronary artery territory. Immediately prior to both ischemia and reperfusion, animals received an intravenous bolus of either ethyl pyruvate (n = 26) or vehicle control (n = 26). Myocardial high-energy phosphate levels were determined by adenosine triphosphate assay, oxidative injury was measured by lipid peroxidation assay, infarct size was quantified by triphenyltetrazolium chloride staining, and cardiac function was assessed in vivo. RESULTS: Ethyl pyruvate administration significantly increased myocardial adenosine triphosphate levels compared with control (87.6 +/- 29.2 nmol/g vs 10.0 +/- 2.4 nmol/g, P =.03). In ischemic myocardium, ethyl pyruvate reduced oxidative injury compared with control (63.8 +/- 3.3 nmol/g vs 89.5 +/- 3.0 nmol/g, P <.001). Ethyl pyruvate diminished infarct size as a percentage of area at risk (25.3% +/- 1.5% vs 33.6% +/- 2.1%, P =.005). Ethyl pyruvate improved myocardial function compared with control (maximum pressure: 86.6 +/- 2.9 mm Hg vs 73.5 +/- 2.5 mm Hg, P <.001; maximum rate of pressure rise: 3518 +/- 243 mm Hg/s vs 2703 +/- 175 mm Hg/s, P =.005; maximal rate of ventricular systolic volume ejection: 3097 +/- 479 microL/s vs 2120 +/- 287 microL/s, P =.04; ejection fraction: 41.9% +/- 3.8% vs 31.4% +/- 4.1%, P =.03; cardiac output: 26.7 +/- 0.9 mL/min vs 22.7 +/- 1.3 mL/min, P =.01; and end-systolic pressure-volume relationship slope: 1.09 +/- 0.22 vs 0.59 +/- 0.2, P =.02). CONCLUSIONS: In this study of myocardial ischemia-reperfusion injury, ethyl pyruvate enhanced myocardial adenosine triphosphate levels, attenuated myocardial oxidative injury, decreased infarct size, and preserved cardiac function.