Preoperative beta-blocker use: is titration to a heart rate of 60 beats per minute a consistently attainable goal?

STUDY OBJECTIVE: To quantify the prevalence of perioperative beta-blocker use and its impact on preoperative and preinduction heart rate (HR), in light of the recent publication of specific recommendations regarding perioperative beta-blocker use and desired HR. DESIGN: Retrospective observational study in patients who underwent elective and coronary artery bypass graft (CABG) surgery between January 2001 and March 2002. SETTING: Tertiary-care teaching hospital. MEASUREMENTS: Percentage of eligible patients who received beta-blockers preoperatively and the impact of non-protocol-based beta-blocker therapy on preadmission and preinduction HR were recorded. Differences were assessed with unpaired t test and chi(2) analysis; P < .05 was considered significant, with corrections for multiple comparisons. RESULTS: Of the patients who underwent vascular surgery, 9 had documented prior beta-blocker intolerance. Of the remaining 172 patients, 94.8% had indication for perioperative beta-blocker use. However, only 47.7% of the eligible patients received beta-blockers. Of the 155 CABG patients, 74.2% were taking beta-blockers preoperatively. Only 29% of vascular patients and 32% of CABG patients who were receiving beta-blockers had HR less than 60 beats per minute (bpm) at preadmission. The mean preadmission HR in vascular surgery patients was 65.2 +/- 11 and 73.2 +/- 13.8 bpm in beta-blocker and non-beta-blocker patients, respectively (P = .0001). In CABG surgery patients, preadmission HR values were 64.2 +/- 13 and 76.1 +/- 12 bpm in beta-blocker and non-beta-blocker patients, respectively (P = .001). The preinduction HR subsequently increased in the beta-blocker as well as in the non-beta-blocker groups. CONCLUSION: Only half of the patients who qualify to receive preoperative beta-blockers by current recommendations actually receive them before noncardiac surgery, and the majority of these patients have preadmission and preinduction HR less than 60 bpm. Targeting beta-blocker therapy treatment to an HR less than 60 bpm may not be readily achievable in many patients.     

The effect of beta-blocker dosing strategy on regulation of perioperative heart rate and clinical outcomes in patients undergoing vascular surgery: a randomized comparison

The optimal dosing strategy for perioperative beta-blockers to safely achieve recommended target heart rates (HRs) by current guidelines is not well defined. An HR-titrated perioperative beta-blocker dosing regimen versus a fixed-dose regimen was assessed by clinical outcomes, postoperative heart rate, and beta-blocker-related complications. Patients (n = 64) scheduled to undergo moderate- to high-risk vascular surgery and without contraindications to beta-blockade were randomized to either a fixed-dose or HR-titrated beta-blocker dosing schedule. Clinical outcomes and HRs were followed immediately preoperatively to 24 hr postoperatively. A difference in mean HR between the two dosing arms was significant immediately postoperatively (70.1 vs. 58.2 bpm for fixed dose and HR-titrated arms, respectively; p = 0.012) but at no other time points. However, the HR-titrated strategy led to a significant reduction in the percentage of HR measurements >80 bpm (34.5% vs. 16.1%, p < 0.001) and to a significant reduction in absolute HR change (17.5 vs. 22.5 bpm, p = 0.034). There were no significant differences in the occurrence of asymptomatic hypotension between the two study arms, and no beta-blocker-related adverse events occurred in either study arm. An aggressive, HR-titrated perioperative beta-blocker dosing strategy was associated with more consistent maintenance of postoperative HRs within the range recommended by current guidelines and did not result in increased drug-related adverse events. The question of what is the best perioperative beta-blocker dosing regimen warrants further evaluation in a large-scale clinical trial.     

Increase of 1-year mortality after perioperative beta-blocker withdrawal in endovascular and vascular surgery patients.

OBJECTIVES: To assess the relation between beta-blocker use, underlying cardiac risk, and 1-year outcome in vascular surgery patients, including the effect of beta-blocker withdrawal. DESIGN: Prospective survey. MATERIALS: 711 consecutive peripheral vascular surgery patients from 11 hospitals in the Netherlands between May and December 2004. METHODS: Patients were evaluated for cardiac risk factors, beta-blocker use and 1-year mortality. Low and high risk was defined according to the Revised Cardiac Risk Index. Propensity scores for the likelihood of beta-blocker use were calculated and regression models were used to study the relation between beta-blocker use and mortality. RESULTS: 285 patients (40%) received beta-blockers throughout the perioperative period (continuous users). Only 52% of the 281 high risk patients received continuous beta-blocker therapy. Beta-blocker therapy was started in 29 and stopped in 21 patients, respectively. One-year mortality was 11%. After adjustment for potential confounders and the propensity of its use, continuous beta-blocker use remained significantly associated with a lower 1-year mortality compared to non-users (HR=0.4; 95%CI=0.2-0.7). In contrast, beta-blocker withdrawal was associated with an increased risk of 1-year mortality compared to non-users (HR=2.7; 95%CI=1.2-5.9). CONCLUSIONS: We demonstrated an under-use of beta-blockers in vascular surgery patients, even in high-risk patients. Perioperative beta-blocker use was independently associated with a lower risk of 1-year mortality compared to non-use, while perioperative withdrawal of beta-blocker therapy was associated with a higher 1-year mortality.     

New index for assessing the chronotropic response in patients with end-stage liver disease who are undergoing dobutamine stress echocardiography

The inability to achieve 85% of the maximum predicted heart rate (MPHR) on dobutamine stress echocardiography (DSE) is defined as chronotropic incompetence and is a predictor of major cardiac events after orthotopic liver transplantation (OLT). The majority of patients with end-stage liver disease (ESLD) receive beta-blockers for the prevention of variceal bleeding. In these patients, it is impossible to determine whether chronotropic incompetence is secondary to cirrhosis-related autonomic dysfunction or is merely a beta-blocker effect. We evaluated the usefulness of the maximum achieved heart rate (MAHR) and the heart rate reserve (HRR) in the detection of chronotropic incompetence in ESLD patients on beta-blocker therapy before DSE. We also evaluated the usefulness of a new index, the modified heart rate reserve (MHRR), in diagnosing chronotropic incompetence and predicting major cardiovascular adverse events after OLT. The study population consisted of 284 ESLD patients. The mean values of MAHR (expressed as a percentage of 85% of MPHR) and HRR were significantly lower for patients on beta-blockers versus patients off beta-blockers [97.1% versus 101.6% (t = 5.01, P < 0.001) and 71.7% versus 77.3% (t = 4.03, P < 0.001), respectively], whereas the values of MHRR were similar in patients on beta-blockers and patients off beta-blockers [102.3% versus 102.1% (t = 0.04, P = 0.97)]. A regression analysis showed a significant association of MAHR (P < 0.001) and HRR (P < 0.001) with beta-blockers, whereas MHRR was not associated with beta-blocker treatment (P = 0.92). MAHR and HRR were found to have no value for diagnosing chronotropic incompetence in ESLD patients. MHRR was not affected by beta-blocker therapy. Patients who developed heart failure (HF) and myocardial infarction (MI) after OLT had significantly lower MHRR values according to pretransplant DSE. MHRR was significantly associated with the subsequent development of HF (P = 0.01) and MI (P = 0.01) after OLT. MHRR may be useful for the determination of the target heart rate for stress testing, the diagnosis of chronotropic incompetence, and the prediction of adverse cardiac events after OLT.     

Postoperative prophylactic administration of beta-adrenergic blockers in patients at risk for myocardial ischemia

Perioperative myocardial ischemia (MI) is associated with postoperative cardiac morbidity. Postoperative sympatholysis may reduce the incidence of MI. This study evaluated such a reduction postoperatively with the administration of prophylactic beta-blockers in patients undergoing elective total knee arthroplasty with epidural anesthesia and postoperative epidural analgesia. One hundred seven patients were preoperatively randomized into two groups, control and beta-blockers, who received postoperative esmolol infusions on the day of surgery and metoprolol for the next 48 h to maintain a heart rate less than 80 bpm. Patients were followed for ST segment depression by using a Holter monitor and adverse cardiac outcomes. Postoperative electrocardiographic ischemia was significantly more prevalent in the control group compared with the beta-blocker group during esmolol blockade (0 of 52 vs 4 of 55; P = 0.04) and tended to be more common in the control group the next two days (8 of 55 vs 3 of 52; P = 0.135). In addition, the number of ischemic events (control, 50; beta-blockers, 16) and total ischemic time (control, 709 min; beta-blocker, 236 min) were also significantly different from the control group. Myocardial infarctions and cardiac events were more common in the control group, but these differences were not significant. Our results suggest that the use of prophylactic beta-blocker therapy may reduce the incidence of postoperative MI. Implications: Prophylactic beta adrenergic blockade administered after elective total knee arthroplasty was associated with a reduced prevalence and duration of postoperative myocardial ischemia detected with Holter monitoring.     

Perioperative beta-blocker therapy and heart rate control during noncardiac surgery

BACKGROUND: Perioperative treatment with beta-blockade is a widely advocated practice. We assessed the preoperative, intraoperative, and postoperative control of heart rate (HR) in patients who received beta-blockade as recommended during preoperative medicine clearance. METHODS: We conducted a retrospective review of patients who underwent noncardiac surgery from 2002 to 2004 at the Michael E. DeBakey Veterans Affairs Medical Center in Houston, Texas, with recommendations of beta-blockade as part of their risk stratification. Demographic data and comorbid risk factors were collected on patients undergoing general anesthesia. All data were presented as mean +/- SEM. The chi-square test and analysis of variance were used for statistical analysis. RESULTS: A total of 130 patients referred for preoperative medicine clearance, who were risk-stratified based on comorbid conditions and risk of procedure, had beta-blockade started before elective surgery. Sixty percent (78 of 130) of the patients underwent high-/intermediate-risk surgery. The mean preoperative HR was 74 +/- 1 beat per minute (bpm). The mean intraoperative HR was 69 +/- 1 bpm. The mean postoperative HR was 84 +/- 1 bpm. There was a significant difference in the preoperative and intraoperative HR when compared with the postoperative HR (P < .003). There were no deaths at 30 days postoperatively. Perioperative cardiac morbidity occurred in 5.4% (7 of 130) of all patients (high patient risk, 71%; low patient risk, 29%; P < .05), and did not correlate with procedure risk. CONCLUSIONS: Beta-blockade is achieved sufficiently in the preoperative and intraoperative settings. However, attention to postoperative HR may be warranted to maintain the benefits of beta-blockade.     

Beta-blockers in isolated blunt head injury

BACKGROUND: The purpose of this study was to evaluate the effect of beta-blockers on patients sustaining acute traumatic brain injury. Our hypothesis was that beta-blocker exposure is associated with improved survival. STUDY DESIGN: The trauma registry and the surgical ICU databases of an academic Level I trauma center were used to identify all patients sustaining blunt head injury requiring ICU admission from July 1998 to December 2005. Patients sustaining major associated injuries (Abbreviated Injury Score > or = 4 in any body region other than the head) were excluded. Patient demographics, injury profile, Injury Severity Score, and beta-blocker exposure were abstracted. The primary outcomes measure evaluated was in-hospital mortality. RESULTS: During the 90-month study period, 1,156 patients with isolated head injury were admitted to the ICU. Of these, 203 (18%) received beta-blockers and 953 (82%) did not. Patients receiving beta-blockers were older (50 +/- 21 years versus 38 +/- 20 years, p < 0.001), had more frequent severe (Abbreviated Injury Score > or = 4) head injury (54% versus 43%, p < 0.01), Glasgow Coma Scale < or = 8 less often (37% versus 47%, p = 0.01), more skull fractures (20% versus 12%, p < 0.01), and underwent craniectomy more frequently (23% versus 4%, p < 0.001). Stepwise logistic regression identified beta-blocker use as an independent protective factor for mortality (adjusted odds ratio: 0.54; 95% CI, 0.33 to 0.91; p = 0.01). On subgroup analysis, elderly patients (55 years or older) with severe head injury (Abbreviated Injury Score > or = 4) had a mortality of 28% on beta-blockers as compared with 60% when they did not receive them (odds ratio: 0.3; 96% CI, 0.1 to 0.6; p = 0.001). CONCLUSIONS: Beta-blockade in patients with traumatic brain injury was independently associated with improved survival. Older patients with severe head injuries demonstrated the largest reduction in mortality with beta-blockade.     

Chronic beta-blocker therapy improves outcome and reduces treatment costs in chronic type B aortic dissection.

OBJECTIVES: To compare the medical treatment of chronic type B aortic dissection with beta-blockers versus other antihypertensive treatments in terms of their requirement for surgical intervention and treatment costs. METHODS: Case records of the 130 patients treated for aortic dissection type B in this unit between 1988 and 1997 were reviewed. Seventy-eight of 130 patients with chronic dissection have received isolated medical treatment. Seventy-one of 78 patients were discharged alive. Fifty-one of 71 received beta-blocker treatment, 20/71 were treated with other antihypertensive drugs. RESULTS: Surgery for aortic dissection became necessary in 20/71 patients (28%) during follow-up (mean, 4.2 years): 10/51 in the beta-blocker group and 9/20 in the other antihypertensive drug group. The freedom from subsequent aortic operation was 80 and 47%, respectively (P=0.001). Indications for emergency surgery were increased aortic diameter (79%), symptomatic aortic aneurysm (11%), and renal artery hypoperfusion (5%). The median hospitalization time during follow-up (dissection-related) was 2 days for patients who received beta-blockers and 16 days for patients who received other antihypertensive drug treatments (P=0.001). The cost of treatment/patient per year amounted to 644 and 12748 euros, respectively. CONCLUSIONS: A substantial proportion of patients with chronic type B dissection who receive initial medical management will later need surgery. Long-term treatment with beta-blockers reduces the progression of aortic dilatation, the incidence of subsequent hospital admissions, as well as the incidence of late dissection-related aortic procedures and the cost of treatment. Patients with chronic type B dissection need, in addition to frequent follow-up of aortic diameter, continuous treatment with beta-blocking agents.     

Heart rate and pulse pressure at rest are major prognostic markers of early postoperative complications after coronary bypass surgery

OBJECTIVE: There is substantial evidence to consider both heart rate (HR) at rest and pulse pressure (PP) as significant markers of cardiovascular prognosis in the general population. Despite this, neither of these two parameters has been taken into consideration in the design of modern coronary artery bypass risk prediction scores, and little data on their early postoperative prognostic value are currently available. We aimed to assess the predictive value of preoperative HR and PP in the 30-day postoperative period. METHODS: We prospectively enrolled all patients referred to our institution for non-urgent coronary artery bypass grafting. We measured HR on ECG at admittance. Preoperative pulse pressure was obtained by the difference of the mean of three consecutive systolic and diastolic blood pressures. The primary outcome combined the 30-day postoperative mortality, myocardial infarction (new Q-waves on ECG or Troponin-I >20 microg/l) and stroke or transient ischemic attack. The secondary outcome corresponded to clinical events only (stroke or death). Statistical analysis was performed by usual methods. RESULTS: We enrolled 1022 patients (age 66.9+/-9.2 years). Those meeting the primary outcome (n=146) had a significantly higher HR (69.9+/-14.3 bpm vs 64.9+/-13.2 bpm, p<0.0001) and a higher proportion presented a PP >70 mmHg (17.1% vs 10.2%, p<0.03). After adjustments for age, gender, systolic blood pressure, preoperative beta-blocker therapy, left ventricular ejection fraction <0.40, unstable cardiac status, redo surgery, peripheral arterial disease, renal failure, and combined vascular surgery, both HR (OR=1.17 per 10 bpm, p<0.03) and PP >70 mmHg (OR=1.99, p=0.03) remained significant risk predictors. Similar results were found when considering only clinical events. CONCLUSION: This prospective study highlights the usefulness of HR and PP as preoperative risk markers in CABG candidates.     

Myocardial beta-blockade as an alternative to cardioplegic arrest during coronary artery surgery.

The authors' recent experimental work has demonstrated that myocardial protection using continuous coronary perfusion with warm beta-blocker-enriched blood avoids myocardial ischaemia and minimizes myocardial oedema formation, thus completely preserving left ventricle function. The purpose of this clinical study was to compare this alternative technique in terms of structural and functional myocardial protection with the routinely used crystalloid Bretschneider cardioplegia. Sixty coronary artery surgery patients were randomized to receive either crystalloid cardioplegia or continuous coronary perfusion with warm blood enriched with the ultra-short acting beta-blocker esmolol. Cardiac function was evaluated using transoesophageal echocardiography (fractional area of contraction) and cardiac metabolism using arterial-coronary sinus lactate concentration difference (a - csD(LAC)). From left ventricular biopsies, the authors determined myocardial oedema, heat-shock-protein-70, intercellular-adhesion-molecule and actin pattern. Patients with crystalloid cardioplegia received 3.6 +/- 0.8 grafts during 64 +/- 20 min cross-clamp time (beta-blocker: 3.5 +/- 0.9 grafts during 68 +/- 22 min; NS). Following cross-clamp removal crystalloid cardioplegia hearts released significant lactate amounts (a- csD(LAC)) - 1.0 +/- 0.6 versus - 0.1 +/- 0.2 mmol/litre in beta-blocker hearts; P < 0.05). In crystalloid cardioplegia hearts, myocardial water content increased from 82.1 +/- 2.1% pre-cardiopulmonary bypass to 83.2 +/- 1.7% at the end of cardiopulmonary bypass (P < 0.05); in beta-blocker hearts myocardial water content remained unchanged (pre-cardiopulmonary bypass: 82.3 +/- 1.9%; end of cardiopulmonary bypass: 82.4 +/- 1.7%; NS). At the end of cardiopulmonary bypass, left ventricular biopsies of beta-blocker hearts showed less structural damage as determined by heat shock protein-70, intercellular adhesion molecule-I and deranged actin cross-striation pattern as compared with crystalloid cardioplegia hearts (P < 0.05). The post-cardiopulmonary bypass fractional area of contraction was similar in both groups (beta-blocker: 65 +/- 14%; crystalloid cardioplegia: 62 +/- 16%); however, beta-blocker patients required less inotropic stimulation (dopamine: beta-blocker: 2.9 +/- 2.5 versus crystalloid cardioplegia: 5.0 +/- 2.3 microg/kg per min; P < 0.05). The data suggest that continuous coronary perfusion with warm esmolol-enriched blood results in better myocardial protection compared with crystalloid cardioplegia. It is concluded that the concept of beta-blocker-induced cardiac surgical conditions may be a useful alternative for myocardial protection during coronary artery surgery.     

Heart rate reduction after heart transplantation with beta-blocker versus the selective If channel antagonist ivabradine

BACKGROUND: Graft denervation in heart transplant recipients causes sinus tachycardia, occasionally requiring pharmacologic heart rate reduction. The If channel antagonist ivabradine has not been compared to beta-blocker after heart transplantation. Heart rate control, tolerability, short-term safety, and effects on exercise capacity were studied consecutively with an established heart rate-reducing drug (metoprolol succinate) compared to a novel agent (ivabradine) in heart transplant recipients. METHODS: In 25 heart transplant recipients, heart rate, exercise capacity, and patient preference were assessed under no medication (baseline) and after consecutive 8-week treatment periods under metoprolol and ivabradine. RESULTS: Drug discontinuation following side effects occurred in 5 patients (metoprolol: 4, ivabradine: 1); per-protocol analysis was performed on 20 patients completing both consecutive treatment periods. Mean heart rate was reduced from baseline (96.5+/-7.0 bpm) to 84.4+/-8.8 bpm on beta-blocker (P=0.0004 vs. baseline) and to 76.2+/-8.9 bpm with ivabradine (P=0.0001 vs. baseline and P=0.003 vs. beta-blocker). Exercise capacity by spiroergometry was not altered by either drug. Relevant pharmacokinetic interaction with immunosuppressants was not seen under ivabradine; safety laboratory values were unchanged. Mild adverse effects were noted in 45% of patients during beta-blocker and 20% during ivabradine treatment. Questionnaire analysis demonstrated patient preference for heart rate reduction with ivabradine. CONCLUSIONS: Heart rate reduction with ivabradine is effective and potentially better tolerated than beta-blocker therapy in heart transplant recipients. Although the prognostic role of heart rate after HTX is unknown, ivabradine may offer relevant symptomatic benefit, especially in cases of beta-blocker intolerance.     

A prospective, randomized comparison between ultrasound and nerve stimulation guidance for multiple injection axillary brachial plexus block

BACKGROUND: This prospective, randomized, blinded study tested the hypothesis that ultrasound guidance can shorten the onset time of axillary brachial plexus block as compared with nerve stimulation guidance when using a multiple injection technique. METHODS: Sixty American Society of Anesthesiology physical status I-III patients receiving axillary brachial plexus block with 20 ml ropivacaine, 0.75%, using a multiple injection technique, were randomly allocated to receive either nerve stimulation (group NS, n = 30), or ultrasound guidance (group US, n = 30) for nerve location. A blinded observer recorded the onset of sensory and motor blocks, the need for general anesthesia (failed block) or greater than 100 microg fentanyl (insufficient block) to complete surgery, procedure-related pain, success rate, and patient satisfaction. RESULTS: The median (range) number of needle passes was 4 (3-8) in group US and 8 (5-13) in group NS (P = 0.002). The onset of sensory block was shorter in group US (14 +/- 6 min) than in group NS (18 +/- 6 min) (P = 0.01), whereas no differences were observed in onset of motor block (24 +/- 8 min in group US and 25 +/- 8 min in group NS; P = 0.33) and readiness to surgery (26 +/- 8 min in group US and 28 +/- 9 min in group NS; P = 0.48). No failed block was reported in either group. Insufficient block was observed in 1 patient (3%) of group US and 2 patients (6%) of group NS (P = 0.61). Procedure-related pain was reported in 6 patients (20%) of group US and 14 patients (48%) of group NS (P = 0.028); patient acceptance was similarly good in the two groups. CONCLUSION: Multiple injection axillary block with ultrasound guidance provided similar success rates and comparable incidence of complication as compared with nerve stimulation guidance.     

A Prospective, Randomized Comparison between Ultrasound and Nerve Stimulation Guidance for Multiple Injection Axillary Brachial Plexus Block

Background: This prospective, randomized, blinded study tested the hypothesis that ultrasound guidance can shorten the onset time of axillary brachial plexus block as compared with nerve stimulation guidance when using a multiple injection technique.

Methods: Sixty American Society of Anesthesiology physical status I-III patients receiving axillary brachial plexus block with 20 ml ropivacaine, 0.75%, using a multiple injection technique, were randomly allocated to receive either nerve stimulation (group NS, n = 30), or ultrasound guidance (group US, n = 30) for nerve location. A blinded observer recorded the onset of sensory and motor blocks, the need for general anesthesia (failed block) or greater than 100 [mu]g fentanyl (insufficient block) to complete surgery, procedure-related pain, success rate, and patient satisfaction.

Results: The median (range) number of needle passes was 4 (3-8) in group US and 8 (5-13) in group NS (P = 0.002). The onset of sensory block was shorter in group US (14 +/- 6 min) than in group NS (18 +/- 6 min) (P = 0.01), whereas no differences were observed in onset of motor block (24 +/- 8 min in group US and 25 +/- 8 min in group NS; P = 0.33) and readiness to surgery (26 +/- 8 min in group US and 28 +/- 9 min in group NS; P = 0.48). No failed block was reported in either group. Insufficient block was observed in 1 patient (3%) of group US and 2 patients (6%) of group NS (P = 0.61). Procedure-related pain was reported in 6 patients (20%) of group US and 14 patients (48%) of group NS (P = 0.028); patient acceptance was similarly good in the two groups.     

Propofol-nitrous oxide anesthesia enhances the heart rate response to intravenous isoproterenol infusion

Heart rate (HR) response to IV atropine is attenuated during propofol-nitrous oxide (N(2)O) anesthesia. We studied the effects of propofol-N(2)O anesthesia on isoproterenol-induced HR changes. The control group (n = 15) received no propofol and no N(2)O. Patients in the propofol-N(2)O group (n = 21) received IV propofol 2.5 mg/kg over 1 min followed by a continuous infusion of propofol 10 mg x kg(-1) x h(-1). After tracheal intubation, anesthesia was maintained with propofol 5 mg. kg(-1) x h(-1) and 67% N(2)O in oxygen. All patients in both groups received IV isoproterenol at incremental infusion rates (2.5, 5, 7.5, 10, 12.5, 15, and 17.5 ng x kg(-1) x min(-1) for 2 min at each dose) until HR increased more than 20 bpm from baseline values. At the end of each infusion period, hemodynamic data were collected. The HR response to isoproterenol 7.5 ng. kg(-1) x min(-1) was increased more in the propofol group than in the control group (20 +/- 5 versus 14 +/- 4 bpm; P < 0.05). During the isoproterenol infusion at 10 ng. kg(-1) x min(-1), HR increased by more than 20 bpm in all patients in the propofol group but in only 31% of patients in the control group (P < 0.0001). These results suggest that continuous isoproterenol infusion might be useful when a large dose of atropine is ineffective in restoring normal HR during propofol-N(2)O anesthesia. IMPLICATIONS: We demonstrated that the heart rate response to IV isoproterenol infusion is enhanced during propofol-nitrous oxide anesthesia. This suggests that continuous isoproterenol infusion may be useful when a large dose of atropine is ineffective for restoration of normal heart rate in patients receiving propofol-nitrous oxide anesthesia.     

Heart failure survival score continues to predict clinical outcomes in patients with heart failure receiving β-blockers

BACKGROUND: The Heart Failure Survival Score (HFSS) has been previously shown to effectively risk-stratify patients under evaluation for heart transplantation. However, this model was developed before broad use of beta blockade. We hypothesized that the prognostic tool would retain its ability to risk stratify patients treated with beta-blockers. METHODS: We collected clinical data on 524 consecutive patients referred for heart transplantation from 1994 to 2001. Kaplan-Meier survival analysis and multivariable Cox regression analysis were performed with events defined as death, left ventricular assist device placement, or United Network of Organ Sharing 1 heart transplantation. RESULTS: Kaplan-Meier analysis of the patient population revealed effective discrimination by the survival score both for beta-blocker treated and untreated patients (both p <0.0001). Two-year event-free survival was 94% +/- 2% and 84% +/- 4% for beta-blocker and no beta-blocker patients in the low-risk HFSS strata. Cox proportional hazard modeling showed that HFSS strata (medium risk: HR 2.65, 95% CI 1.75-4.02, p <0.001; high risk: HR 5.51, 95% CI 3.64-8.33, p <0.001) and beta-blocker treatment (HR 0.45, 95% CI 0.31-0.64, p <0.001) were significant predictors of event-free survival. Receiver operating curves (area under the curve) for HFSS strata used to predict 2-year events were similar for beta-blocker treated (0.78 +/- 0.04) and untreated (0.80 +/- 0.03) patients. CONCLUSIONS: The HFSS provides effective risk stratification with or without beta-blocker therapy. Consideration of beta-blocker therapy with survival score strata improves outcome prediction in patients evaluated for heart transplantation.     

Beta-blockers improve in-hospital and long-term survival in patients with severe left ventricular dysfunction undergoing major vascular surgery.

OBJECTIVES: To study whether beta-blockers reduce in-hospital and long-term mortality in patients with severe left ventricular dysfunction (LVD) undergoing major vascular surgery. DESIGN: Observational cohort study. MATERIALS: Five hundred and eleven patients with severe LVD (ejection fraction<30%) undergoing major non-cardiac vascular surgery. METHODS: In all patients, cardiac risk factors, medication (including beta-blockers), and dobutamine stress echocardiography (DSE) results were noted prior to surgery. DSE was evaluated for rest and stress-induced new wall motion abnormalities. Endpoint was in-hospital and long-term mortality. Propensity scores for beta-blockers were calculated and regression models were used to analyse the relation between beta-blockers and mortality. RESULTS: Mean age was 64+/-11 years and 383 patients (75%) were male. 139 patients (27%) used beta-blockers. Stress-induced ischemia occurred in 82 patients (16%). Median follow-up was 7 years (interquartile range: 3-10). In-hospital and long-term mortality was observed in 64 (13%) and 171 (33%) patients, respectively. After adjusting for clinical variables, DSE results and propensity scores, beta-blockers were significantly associated with reduced in-hospital and long-term mortality (OR: 0.18, 95% CI: 0.04-0.74 and HR: 0.38, 95% CI: 0.22-0.65, respectively). CONCLUSION: In patients with severe LVD undergoing major vascular surgery, the use of beta-blockers is associated with a reduced incidence of in-hospital and long-term postoperative mortality.     

Ephedrine, dopamine, or doubtamine to treat hypotension with propofol during epidural anesthesia

PURPOSE: To compare the efficacy of ephedrine, dopamine and dobutamine for circulatory support during thoracic epidural anesthesia after anesthetic induction with propofol. METHODS: Forty patients undergoing lobectomy or mastectomy were divided into four groups of 10: a control group received no vasopressor; an ephedrine group received 5 mg ephedrine when the mean arterial pressure (MAP), measured every 2.5 min, decreased by 10% from baseline; dopamine and dobutamine groups received 5 microg x kg(-1) x min(-1) dopamine or 3 microg x kg(-1) x min(-1) dobutamine from five minutes after epidural injection of local anesthetic to the end of tracheal intubation. Anesthesia was induced with 2 mg x kg(-1) propofol. The MAP and heart rate (HR) were measured at baseline, 20 min after epidural injection, three minutes after propofol, and one minute after tracheal intubation. RESULTS: In the control group, MAP and HR decreased from 86+/-9 mmHg, 74+/-8 bpm to 62+/-9 mm Hg; P<0.0001, 60+/-8 bpm; P = 0.0003 after propofol. After tracheal intubation, MAP was restored to (81+/-13 mmHg, 70+/-13 bpm). In the ephedrine, dopamine, and dobutamine groups, MAP and HR remained unchanged during epidural anesthesia and propofol induction. However, after tracheal intubation, MAP and HR increased in the ephedrine (104+/-11 mm Hg; P = 0.004, 87+/-11 bpm; P<0.0001) and dobutamine (117+/-13 mm Hg; P = 0.0005, 100+/-11 bpm; P<0.0001) groups, but not in the dopamine group compared with baseline. CONCLUSION: Dopamine is preferable to ephedrine and dobutamine in providing hemodynamic stability during propofol induction and tracheal intubation following epidural anesthesia.     

Exercise assessment in infants after cardiac transplantation

BACKGROUND: Few data describe exercise performance after cardiac transplantation during infancy. The aim of this study was to compare the cardiorespiratory response to exercise in healthy subjects with that of subjects who had undergone heart transplantation during infancy to treat hypoplastic left heart syndrome. METHODS: Subjects (24 heart transplant recipients and 25 healthy controls) exercised on a treadmill using pediatric ramp protocols. We measured heart rate (HR), blood pressure, and metabolic data. Median age at transplantation was 20 days (range, 4 to 97 days). Age of recipients at exercise testing was 9.7 +/- 2.3 years and in healthy subjects was 10.5 +/- 1.4 years (p=not significant [NS]). RESULTS: Exercise duration was similar in both groups (10.3 +/- 2.0 minutes in recipients vs 11.1 +/- 1.5 minutes in healthy subjects, (p=NS). Heart rate at rest was greater in recipients (94 +/- 15 beats per minute [bpm] vs 85 +/- 11 bpm, p=0.02). Peak HR also was less in the recipient group (158 +/- 15 bpm vs 189 +/- 12 bpm, p <0.001). Peak oxygen consumption was 14% less in the recipients (32.3 +/- 5.6 ml/kg/min vs 36.8 +/- 5.5 ml/kg/min, p <0.01). Ventilatory anaerobic threshold was decreased in recipients, 27.6 +/- 9.6 vs 32.8 +/- 6.0, p <0.05. Respiratory exchange ratio at peak exercise was equal in both groups (1.06 +/- 0.06 vs 1.06 +/- 0.08). Oxygen pulse index did not differ significantly, 5.5 +/- 1.1 ml/beat/m2 in recipients and 6.1 +/- 1.7 ml/beat/m2 in healthy subjects (p=NS). CONCLUSIONS: Overall, children who undergo cardiac transplantation in infancy have exercise capacities within the normal range. These recipients have a decreased heart rate reserve that may account for the differences in peak oxygen consumption when compared with healthy subjects.     

Randomised, placebo-controlled study of the postoperative analgesic effects of ketoprofen after spinal fusion surgery

BACKGROUND: The additive effect of non-steroidal anti-inflammatory drugs administered with propacetamol after major orthopaedic surgery has not been studied. Thus, we performed a prospective, placebo-controlled study to assess the analgesic effects of ketoprofen in patients undergoing spinal fusion surgery and receiving propacetamol. METHODS: Fifty patients undergoing spinal fusion surgery received either 100 mg of ketoprofen every 8 h or a placebo, postoperatively. All patients received propacetamol and morphine (intravenous titration followed by patient-controlled analgesia (PCA) over 24 h). Pain was assessed using a visual analogue pain scale (VASpi). Data are mean+/-SD. RESULTS: During morphine titration, ketoprofen did not significantly reduce the dose of morphine (8+/-6 vs 11+/-4 mg, NS) whereas it significantly decreased VASpi (P<0.001). During PCA, ketoprofen significantly reduced morphine consumption (25+/-17 vs 38+/-20 mg, P=0.04) and VASpi (P=0.002). The total postoperative morphine consumption was significantly (33%) reduced with ketoprofen. CONCLUSION: Ketoprofen reduced morphine requirements and improved postoperative analgesia in patients undergoing major spinal surgery and receiving propacetamol.     

Haemodynamic and catecholamine responses to calcitonin gene-related peptide during volatile anaesthesia

PURPOSE: Calcitonin gene-related peptide (CGRP) produces vasodilatation, hypotension, and tachycardia. Tachycardia induced by CGRP may be due to sympathetic activation. Volatile anaesthetics attenuate activation of arterial baroreflexes. We examined the haemodynamic and endocrine effects of CGRP infusion (4 micrograms.kg-1) during anaesthesia with either enflurane or isoflurane in dogs. METHODS: Measurements of haemodynamic variables and hormone assays for plasma catecholamines were made before, during, and after CGRP infusion. Anaesthesia consisted of induction with 25 mg.kg-1 pentobarbital, followed by either enflurane (n = 7) or isoflurane (n = 7) to achieve a 1.0 end-tidal minimum alveolar concentration in oxygen 100%. RESULTS: Mean arterial pressure and systemic vascular resistance decreased (P < 0.01) and the reductions in both variables were similar during CGRP infusion in both groups. Cardiac index (CI) was increased (P < 0.01) in the enflurane group throughout the study while CI increased (P < 0.01) only during infusion in the isoflurane group. Heart rate (HR) remained unchanged (from 135 +/- 6 bpm to 134 +/- 7 bpm) in the enflurane group but tended to increase (from 162 +/- 9 bpm to 171 +/- 9 bpm) in the isoflurane group during infusion. Intergroup differences in HR were found (P < 0.05). Plasma epinephrine concentrations increased (from 42.4 +/- 12.7 pg.ml-1 to 115.3 +/- 41.8 pg.ml-1, P < 0.01) during infusion in the isoflurane group. However, these increases were suppressed (from 46.6 +/- 23.2 pg.ml-1 to 64.7 +/- 32.4 pg.ml-1) to a greater extent in the enflurane group. CONCLUSION: The haemodynamic responses, except for HR, of CGRP infusion are similar during enflurane and isoflurane anaesthesia. Suppression of tachycardia induced by CGRP is greater with enflurane than with isoflurane. The differences in HR may be due to the roles of catecholamine responses resulting from the anaesthetic-induced sympathetic suppression.