Roger L. Royster

Effects on intracranial pressure of resuscitation from hemorrhagic shock with hypertonic saline versus lactated Ringer's solution.

Hypertonic saline (2400 mOsm/L) has been used successfully for fluid resuscitation of dogs subjected to severe hemorrhagic shock. This study compared the effects of resuscitation with hypertonic saline vs. lactated Ringers solution on intracranial pressure (ICP) in dogs subjected to 30 min of sustained hypovolemic shock. Hypotension was produced by rapid withdrawal of blood until mean arterial pressure was 50 mm Hg, maintained at that level by withdrawal or infusion of blood over the next 30 min as necessary. Eight animals were resuscitated with hypertonic saline solution and nine with lactated Ringers solution. Both solutions restored systolic blood pressure and cardiac output to control values. However, diastolic blood pressure and mean arterial pressure did not return to control values. The most prominent difference between the two groups was in ICP measured after resuscitation. ICP was lower in dogs resuscitated with hypertonic saline than in dogs resuscitated with lactated Ringers solution (p = .029). Hypertonic saline fluid resuscitation may represent a potential alternative when aggravation of intracranial hypertension during resuscitation would place a patient at greater risk.

Coronary artery stents: II. Perioperative considerations and management.

The management of patients with coronary artery stents during the perioperative period is one of the most important patient safety issues clinicians confront. Perioperative stent thrombosis is a life-threatening complication for patients with either bare-metal or drug-eluting stents. Noncardiac surgery appears to increase the risk of stent thrombosis, myocardial infarction, and death, particularly when patients undergo surgery early after stent implantation. The incidence of complications is further increased when dual-antiplatelet therapy is discontinued preoperatively. It is generally agreed that aspirin must be continued throughout the perioperative period, except in circumstances when the risk of bleeding significantly outweighs the benefit of continued anticoagulation, such as procedures performed in a closed space. We present considerations for regional anesthesia, as well as postoperative recommendations as the occurrence of perioperative stent thrombosis appears to be greatest during this period. Immediate percutaneous coronary intervention is the definitive treatment for perioperative stent thrombosis, and 24-h access to an interventional cardiology suite should be readily available. Algorithms for perioperative management of patients with bare-metal and drug-eluting stents are proposed.

Preoperative and intraoperative predictors of inotropic support and long-term outcome in patients having coronary artery bypass grafting.

The prognostic value of preoperative symptoms, preoperative left ventricular function, and intraoperative factors as related to postoperative outcome in coronary artery bypass grafting is unclear. This study was performed to identify risk factors that could be used as markers to predict immediate and long-term outcome, knowledge of which might allow physicians to modify these factors to decrease the likelihood of an adverse outcome. We retrospectively evaluated preoperative factors (including age, sex, New York Heart Association [NYHA] classification of symptoms, ejection fraction [EF], wall motion abnormalities, baseline left ventricular end-diastolic pressure [LVEDP], postradiographic contrast infection LVEDP, change in LVEDP with contrast injection, cardiac enlargement, and collateral vessels) and intraoperative factors (duration of bypass and aortic cross-clamp time) in 128 patients. The need for inotropic drug support was used as a marker of immediate outcome. A 36-mo follow-up used death and the postoperative NYHA classification of symptoms as markers of long-term outcome. The various factors associated with the use of inotropes and immediate outcome were analyzed by logistic regression. The factors related to inotrope use (and presumed adverse short-term outcome) in order of decreasing significance were lower EF, older age, cardiac enlargement, female sex, and higher baseline and postcontrast LVEDP. Patients with EF s 55%, but also having wall motion abnormalities and LVEDP change ≥ 10 mm Hg, and all patients with EF ≥ 55% were more likely to require inotropic drug stimulation after cardiopulmonary bypass. Neither the change in LVEDP nor the presence of wall motion abnormalities independently predicted the need for postoperative inotropic support. Analysis of long-term outcome in 113 patients revealed an improvement in mean NYHA score from 2.8 ± 0.9 (mean ± SD) preoperatively to 1.6 ± 0.7 postoperatively. Those factors that predicted a worse long-term outcome (defined as higher postoperative NYHA scores or death) were higher preoperative NYHA scores, older age, female sex, and prolonged duration of cardiopulmonary bypass. Only 5 of 113 patients had died at the 36-mo follow-up, precluding statistical analysis of mortality. In contrast to randomized trials of oral inotropic agents in chronic congestive heart failure, in this study the perioperative use of inotropes (our marker of immediate outcome) was only marginally predictive of a less favorable long-term outcome.

A Pharmacokinetic and Pharmacodynamic Evaluation of Milrinone in Adults Undergoing Cardiac Surgery

Milrinone can reverse acute postischemic myocardial dysfunction after cardiopulmonary bypass, although neither the appropriate bolus dose nor its pharmacokinetics has been established for cardiac surgical patients.Consenting patients undergoing cardiac surgery received milrinone (25, 50, or 75 micro gram/kg) in an openlabel, dose-escalating study if their cardiac index was <3 L centered dot min-1 centered dot m-2 after separation from bypass. Heart rate, mean arterial blood pressure, pulmonary capillary wedge pressure, and cardiac index were determined before and after the administration of milrinone. Timed blood samples were obtained for measurement of milrinone plasma concentrations and pharmacokinetic analysis. Twenty-nine of 60 consenting patients had cardiac indices <3 L centered dot min-1 centered dot m-2 after separation from bypass, received milrinone, and completed the protocol. All three bolus doses of milrinone significantly increased cardiac index. The 50- and 75-micro gram/kg doses produced significantly larger increases in cardiac index than the 25-micro gram/kg dose; however, the 75-micro gram/kg dose did not produce a significantly larger increase in cardiac index than did the 50-micro gram/kg dose. Two of 10 patients receiving milrinone 25 micro gram/kg, but no patient receiving either 50 or 75 micro gram/kg, required early epinephrine rescue when the cardiac index failed to increase by >15%. The 75-micro gram/kg dose was associated with a case of ventricular tachycardia. The three-compartment model better described milrinone drug disposition than the two-compartment model by both visual inspection and Schwartz-Bayesian criterion. There was only limited evidence of dose-dependence, so data from all three doses are reported together (and normalized to the 50-micro gram/kg dose). Data from one patient was discarded (samples mislabeled). Using mixed-effects nonlinear regression (for n = 28), the following volumes were determined for the three compartments: V (1) = 11.1 L, V2 = 16.9 L, and V3 = 363 L. Similarly, the following clearances were estimated for the three compartments: Cl1 = 0.067 L/min, Cl2 = 1.05 L/min, and Cl3 = 0.31 L/min. The 50-micro gram/kg loading dose appeared more potent than the 25-micro gram/kg dose, and, as potent, but with possibly fewer side-effects than the 75-micro gram/kg dose. The short context-sensitive half-times of 6.7 or 10.2 min after 1- or 10-min bolus infusions underscore the need for prompt institution of a maintenance infusion when milrinone concentrations must be maintained. Simulations based on our best drug disposition using this studys variables predict a context-sensitive half-time of 4.9 h for plasma milrinone concentrations after a 50-micro gram/kg bolus 1-min infusion with an immediate 24-h maintenance infusion of 0.5 micro gram centered dot min-1 centered dot kg-1. (Anesth Analg 1995;81:783-92)

Coronary artery stents: Part I. Evolution of percutaneous coronary intervention.

The subspecialty of interventional cardiology has made significant progress in the management of coronary artery disease over the past three decades with the development of percutaneous coronary transluminal angioplasty, atherectomy, and bare-metal and drug-eluting stents (DES). Bare-metal stents (BMS) maintain vessel lumen diameter by acting as a scaffold and prevent collapse incurred by angioplasty. However, these devices cause neointimal hyperplasia leading to in-stent restenosis and requiring reintervention in more than 20% of patients by 6 mo. DES (sirolimus and paclitaxel) prevent restenosis by inhibiting neointimal hyperplasia. However, DESs also delay endothelialization, causing the stents to remain thrombogenic for an extended, yet unknown, period of time. Late stent thrombosis is associated with a 45% mortality rate. Premature discontinuation of antiplatelet therapy, particularly clopidogrel, is the strongest predictor of stent thrombosis. Sixty percent of patients receive stents for off-label (unapproved) indications, which also increases the frequency of stent thrombosis. Clopidogrel and aspirin are the cornerstone of therapy in the prevention of stent thrombosis in both BMS and DES. Recommendations pertaining to the optimal duration of dual-antiplatelet therapy have been debated. Both the Food and Drug Administration and the American Heart Association/American College of Cardiologists, in association with other major societies, have made recommendations to extend the duration of dual-antiplatelet therapy in patients with DES to 1 yr. The 6-wk duration of dual-antiplatelet therapy in patients with BMS remains unchanged. All patients with coronary stents must remain on life-long aspirin monotherapy. Since the introduction of percutaneous transluminal coronary angioplasty for the treatment of coronary atherosclerosis, the practice of percutaneous coronary intervention has undergone a dramatic transformation from simple balloon dilation catheters to sophisticated mechanical endoprostheses. These advancements have impacted the practice of perioperative medicine. In this series of two articles, in Part I we will review the evolution of percutaneous coronary intervention and discuss the issues associated with percutaneous transluminal coronary angioplasty and coronary stenting; in Part II we will discuss perioperative issues and management strategies of coronary stents during noncardiac surgery.

Factors that predict the use of positive inotropic drug support after cardiac valve surgery.

Left ventricular dysfunction is common after cardiac surgery and is often treated with positive inotropic drugs (PIDs).We hypothesized that the use of PIDs after cardiac valve surgery would have significant associations with the valvular pathophysiology and surgical procedure, and unlike the case for patients undergoing coronary artery surgery, would be unrelated to duration of cardiopulmonary bypass (CPB) or of aortic clamping. One hundred forty-nine consenting patients undergoing cardiac valve surgery were studied. Patients with hepatic or renal failure, or New York Heart Association class IV cardiac symptoms, were excluded. Patients were considered to have received PIDs if they received an infusion of amrinone, dobutamine, epinephrine, or dopamine (>or=to5 [micro sign]g [center dot] kg-1 [center dot] min-1). PIDs were received by 78 patients (52%). In a univariate model, older age, history of congestive heart failure, decreasing left ventricular ejection fraction, longer durations of CPB, and concurrent coronary artery surgery significantly increased the likelihood of PID support. There was also significant variation by anesthesiologist in the administration of PIDs. The specific diseased valve and valvular stenosis or insufficiency did not influence the likelihood of receiving PID support. In a multivariable model, age, history of congestive heart failure, decreasing left ventricular ejection fraction, and anesthesiologist were significantly associated with the likelihood of PID support, but duration of CPB and concurrent coronary artery surgery were not. In conclusion, patient age and ventricular function, as well as physician preferences, predicted the need for inotropic drug support; however, neither the specific valvular lesion, nor duration of CPB were strongly predictive in a multivariable model. Implications: We evaluated factors related to use of positive inotropic drugs after cardiac valve surgery. The likelihood of a patient receiving these drugs increases with advancing age and with more severe preoperative left ventricular dysfunction, but was not influenced by the specific diseased valve or the duration of cardiopulmonary bypass. (Anesth Analg 1998;86:461-7)

The importance of the postoperative anesthetic visit : Do repeated visits improve patient satisfaction or physician recognition ?

This study evaluates whether repeated postoperative visits by the anesthesiologist improve patient ability to recall the anesthesiologists name and the patients perception of and satisfaction with anesthesia services.In a randomized, prospective trial, 144 patients with an anticipated postoperative length of stay of at least three days were enrolled in three groups: Group A patients (n = 48) had one postoperative visit, Group B (n = 48) had two postoperative visits, and Group C (n = 48) had three postoperative visits. All postoperative visits were performed by the attending anesthesiologist on consecutive postoperative days. Patients were contacted two days after their last postoperative visit to complete a study questionnaire. Patients were able to recall the anesthesiologists name significantly less frequently than the surgeons name, and there was no difference in name recall among groups. Recall was not affected by patient age, sex, or ASA physical status; the mode of contact (telephone versus personal visit); the anesthesiologists gender; the presence of preoperative medication; or the identity of the preoperative evaluator. Patients could identify the anesthesiologists gender approximately 85% of the time, regardless of group, and were more likely to identify female anesthesiologists (P = 0.026, odds ratio 3.3). Patient evaluation of hospital, surgical, and anesthesia care was favorable in all groups and did not vary with group. Increasing the number of postoperative visits does not improve patient name recognition of the anesthesiologist or increase patient satisfaction with or perception of anesthesia services. (Anesth Analg 1996;83:793-7)

Combined inotropic effects of amrinone and epinephrine after cardiopulmonary bypass in humans

Amrinone, a phosphodiesterase inhibitor, and epinephrine, an alpha- and beta-adrenergic receptor agonist, are inotropic drugs used during cardiac surgery to reverse myocardial depression after cardiopulmonary bypass. However, these drugs have not been compared separately, or in combination, in this patient population. We hypothesized that the combination might have complementary actions in improving myocardial function. We, therefore, compared amrinone, epinephrine, and the combination of amrinone and epinephrine in a randomized, blinded, placebo-controlled study in patients undergoing coronary artery bypass grafting. Forty patients with ejection fractions > 0.45 were studied. Right ventricular ejection fraction pulmonary artery catheters and radial arterial catheters were inserted before fentanyl-midazolam anesthesia. After separation from bypass, patients received either a placebo (n = 20) or amrinone bolus (1.5 mg/kg, n = 20) at time 0 and a placebo (n = 20) or epinephrine (30 ng.kg-1.min-1, n = 20) infusion at time 5 min. This resulted in four study groups, n = 10 in each group. Data were collected every 2.5 min for 10 min. Epinephrine, amrinone, and the combination of both drugs significantly increased cardiac output, stroke volume, O2 delivery, and left ventricular stroke work. The increase in stroke volume (P < 0.05) was 12 +/- 6, 16 +/- 4, and 30 +/- 4 mL/beat with epinephrine, amrinone, and the combination of amrinone and epinephrine, respectively. The amrinone-epinephrine combination increased stroke volume as much as the sum of amrinone and epinephrine given separately. Systemic vascular resistance and pulmonary vascular resistance decreased with amrinone and amrinone-epinephrine, but not with epinephrine. Epinephrine increased mean arterial and mean pulmonary arterial pressures. Right ventricular ejection fraction did not significantly increase (P = 0.09) with epinephrine, but increased significantly with amrinone (0.45 to 0.53, P = 0.01), and with the combination (0.43 to 0.55, P = 0.006). These data indicate that amrinone and epinephrine effectively increase myocardial performance during cardiac surgery. Right ventricular function especially was improved with amrinone and the combination of amrinone and epinephrine. The combined effects of amrinone and epinephrine may be useful in patients recovering from the ischemia and reperfusion injury resulting from coronary artery bypass grafting.

A randomized, blinded, placebo-controlled evaluation of calcium chloride and epinephrine for inotropic support after emergence from cardiopulmonary bypass

Forty hemodynamically stable patients were randomized to receive an intravenous bolus of either calcium chloride (5 mg/kg) (n = 20) or placebo (n = 20) (phase I). Six minutes later, they received either an epinephrine (30 ng.kg-1.min-1) (n = 20) or placebo (n = 20) infusion (phase II). Hemodynamic and ionized calcium measurements were obtained in phase I at baseline and at 3 and 6 min after the bolus, and in phase II, at 3 and 6 min (study times 9 and 12 min) after initiation of the infusion. Compared with placebo, calcium did not significantly increase cardiac index but significantly increased mean arterial pressure. Calcium improved cardiac index from 2.46 +/- 0.12 (mean +/- SEM) to 2.74 +/- 0.12 L.min-1.m-2; likewise, placebo improved cardiac index from 2.51 +/- 0.15 to 2.74 +/- 0.15 L.min-1.m-2. Mean arterial blood pressure increased with calcium from 74 +/- 2 to 82 +/- 3 mm Hg compared with a placebo change of 74 +/- 2 to 76 +/- 2 mm Hg. Patients who received the epinephrine infusion (n = 20) demonstrated a significant increase in cardiac index at time 12 min compared with patients receiving only placebo (n = 20). Cardiac index of the epinephrine group increased from 2.56 +/- 0.15 to 2.92 +/- 0.22 L.min-1.m-2, whereas in the placebo group it decreased from 2.86 +/- 0.13 to 2.78 +/- 0.12 L.min-1.m-2. Prior administration of calcium did not alter the subsequent response to epinephrine (n = 10) compared with patients receiving epinephrine alone (n = 10). We conclude that cardiac index improves with time without drug therapy after bypass. Calcium chloride increases mean arterial blood pressure but not cardiac index immediately after cardiopulmonary bypass, whereas low-dose epinephrine significantly increases both cardiac index and mean arterial blood pressure without causing tachycardia in these patients. Calcium chloride (5 mg/kg) did not augment or inhibit the hemodynamic response to an epinephrine infusion.

A Multicenter, Randomized, Blind Comparison of Amrinone with Milrinone After Elective Cardiac Surgery

Amrinone and milrinone are phosphodiesterase inhibitors with positive inotropic effects useful for the treatment of ventricular dysfunction after cardiac surgery.Forty-four patients undergoing elective cardiac surgery at four centers received either amrinone (n = 22) or milrinone (n = 22) in a randomized, blind fashion. Immediately after separation from cardiopulmonary bypass (CPB), two bolus doses of either amrinone 0.75 mg/kg or milrinone 25 [micro sign]g/kg were administered over 30 s, separated by 5 min. Hemodynamic measurements were recorded before each dose and at the end of the 10-min study. Both amrinone and milrinone increased the cardiac index (48% vs 52%, P = not significant [NS] for amrinone and milrinone, respectively). There was a small increase in mean arterial pressure (MAP) after amrinone administration (from 68 +/- 3 to 72 +/- 3 mm Hg at 10 min, P < 0.05) with no significant change in MAP after milrinone administration. Central venous pressure was significantly higher in the amrinone group at baseline and 5 min (12 vs 10 mm Hg and 11 vs 10 mm Hg, respectively; P < 0.05). Systemic and pulmonary vascular resistances decreased significantly and to a similar extent after either amrinone or milrinone administration. Phenylephrine was required in 11 of 22 patients receiving amrinone and in 11 of 22 patients receiving milrinone to maintain arterial blood pressure. The proportion of patients requiring an intravascular volume infusion (15 of 22 vs 17 of 22, P = NS) and the total fluid volume infused were similar (402 +/- 57 vs 350 +/- 49 mL, P = NS for amrinone and milrinone, respectively). Amrinone and milrinone seem to have similar hemodynamic effects after CPB, with the exception of blood pressure, although the need for vasopressor support of blood pressure did not differ. Selection between these two drugs may include nonhemodynamic considerations such as cost. Implications: Amrinone and milrinone are drugs that improve cardiac contraction. Their effects have never been directly compared in patients. We found that amrinone and milrinone produced similar hemodynamic effects in adult patients undergoing cardiac surgery. Choice between the two drugs can be based on nonhemodynamic considerations such as cost. (Anesth Analg 1998;86:683-90)