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Biomedical subjects

John Butterworth

Publications and source records attributed to John Butterworth.

At least 19 recordsLinked to original sources

Perioperative management of chronic heart failure.

Heart failure (HF) is one of the few cardiac conditions that is increasing. Despite a better understanding of how hormones and other signaling systems underlie the pathophysiology, and despite improved outcomes from pharmacologic therapy, many HF patients receive no effective treatment. Patients with HF commonly require medical diagnosis and management in operating rooms and critical care units; thus anesthesiologists are obliged to remain up-to-date both with advances in outpatient (chronic) medical management and with inpatient treatments for acute exacerbations of HF. Accordingly, we reviewed angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, beta-adrenergic receptor blockers, and aldosterone antagonists because these drugs prolong life and are included in current clinical practice guidelines for treating patients with chronic HF. We also reviewed the implications of chronic HF for patients undergoing surgery and anesthesia and discuss how best to provide intensive treatment for acute exacerbations of symptoms, such as might be caused by excessive intravascular volume, inappropriate drug "holidays," or worsening of the underlying cardiac disease.

Adrenergic beta-Antagonists↗

Attempted control of hyperglycemia during cardiopulmonary bypass fails to improve neurologic or neurobehavioral outcomes in patients without diabetes mellitus undergoing coronary artery bypass grafting.

OBJECTIVE: Hyperglycemia worsens outcomes in critical illness. This randomized, double-blind, placebo-controlled clinical trial tested whether insulin treatment of hyperglycemia during cardiopulmonary bypass would reduce neurologic, neuro-ophthalmologic, and neurobehavioral outcomes after coronary artery bypass grafting. METHODS: Three hundred eighty-one nondiabetic patients undergoing isolated coronary artery bypass grafting were given infusions of insulin or placebo when their blood glucose concentration exceeded 100 mg/dL during cardiopulmonary bypass. The primary outcome measure was the combined incidence of new neurologic, neuro-ophthalmologic, or neurobehavioral deficits or neurologic death observed at 4 to 8 days postoperatively. This same measure was assessed secondarily at 6 weeks and 6 months. Length of hospital stay was also compared as a secondary assessment. RESULTS: The 2 groups were well matched at baseline. The insulin-treated group had significantly lower blood glucose concentrations during bypass. Sixty-six percent of subjects in the insulin-treated group and 67% of subjects in the control group demonstrated a new or worsening neurologic, neuro-ophthalmologic, or neurobehavioral deficit or neurologic death at the 4- to 8-day assessment. Outcomes were also similar in the 2 groups at 6 weeks (37% and 39% incidence, respectively) and 6 months (30% and 25%, respectively). Median lengths of stay were 7 and 6 days, respectively, in the treatment and control groups. None of these outcome differences was statistically significant. CONCLUSION: Attempted control of hyperglycemia during cardiopulmonary bypass had no significant effect on the combined incidence of neurologic, neuro-ophthalmologic, or neurobehavioral deficits or neurologic death and failed to shorten the length of hospital stay. These results do not contradict those of other studies showing that aggressive control of hyperglycemia in the postoperative period will improve outcome.

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Failure of argatroban anticoagulation during off-pump coronary artery bypass surgery.

Heparin-induced antibodies create vexing problems during cardiac surgery. Although alternative medications have been used for intraoperative anticoagulation, the results have been sufficiently variable that no one medication is recommended. In our case, due to the poor reversibility of the antithrombin agents, argatroban was chosen as a heparin substitute due to its short half-life and its anticoagulation assessment using the activated clotting time (ACT). Unfortunately, our experience was that argatroban does not provide adequate anticoagulation during off-pump coronary bypass surgery, even when the ACT is maintained at more than 380 sec.

Aged↗

Intrathecal morphine reduces infarct size in a rat model of ischemia-reperfusion injury.

UNLABELLED: Systemically-administered morphine reduces infarct size in rat models of myocardial ischemia-reperfusion. We sought to determine whether much smaller doses of spinally-administered morphine offer a similar cardioprotective benefit. Barbiturate-anesthetized, open-chested, Wistar rats with chronic indwelling thoracic intrathecal catheters were instrumented for hemodynamic measurements and subjected to 30 min of coronary occlusion and 90 min of reperfusion. Myocardial infarct size was determined using triphenyl-tetrazolium staining. Rats were randomly assigned to receive intrathecal (IT) 0.9% saline (vehicle), IV morphine (0.3 mg/kg) plus IT saline, small-dose IT morphine (0.3 microg/kg), or large-dose IT morphine (3 microg/kg) 20 min before occlusion. IV and both doses of IT morphine reduced infarct size, defined as area of necrosis expressed as a percentage of area at risk (%AN/AAR), as compared with vehicle. The %AN/AAR group means were as follows: IV (n = 7), 30% +/- 6%; IT(small-dose) (n = 9), 30% +/- 5%; IT(large-dose) (n = 9), 18% +/- 4%; and vehicle (n = 10), 47% +/- 5%. There were no significant differences in infarct size among the morphine-pretreated rats. During ischemia-reperfusion, heart rate was unchanged from baseline in the IT(large-dose) group, whereas in the IT(small-dose), IV and vehicle groups, significant declines in heart rate occurred. Changes in arterial blood pressure were similar among groups. These results indicate that IT morphine reduces infarct size in rats, and this benefit is as great as that provided by IV morphine administration. IMPLICATIONS: Our findings suggest that spinally-administered morphine provides a previously unrecognized cardioprotective benefit. In anesthetized rats subjected to ischemia-reperfusion injury, we show that very small doses of intrathecal morphine reduce infarct size in rats, and this benefit is as great as that provided by much larger doses of IV morphine.

Animals↗

Severe acute visceral pain from varicella zoster virus.

UNLABELLED: Varicella zoster virus infection often will not present in the characteristic dermatomal distribution of vesicles in patients who have undergone bone marrow transplantation. We cared for a 51-yr-old man with severe abdominal pain after bone marrow transplantation for non-Hodgkin's lymphoma. The diagnosis of varicella zoster was not entertained until he developed a diffuse vesicular rash several days after the onset of pain. We report this case to alert others who may be consulted regarding pain management options for similar oncology patients. IMPLICATIONS: We report a patient with lymphoma, prior bone marrow transplant, and acute visceral pain for whom IV opioids in large doses proved inadequate. An interventional pain management technique was considered until characteristic varicella vesicles appeared over the patient's trunk. We report this case to alert others who treat oncology patients that the diagnosis of visceral zoster should be considered when patients who have undergone bone marrow transplantation present with severe visceral pain.

Abdomen↗

Rapid disappearance of protamine in adults undergoing cardiac operation with cardiopulmonary bypass.

BACKGROUND: Despite long use of protamine in cardiac operations, neither protamine concentrations nor pharmacokinetics have been reported in patients. METHODS: Twenty-eight patients (age, 26 to 80 years) undergoing various cardiac surgical procedures gave their consent to receive 250 mg of protamine sulfate administered intravenously by an infusion pump during 5 minutes. Protamine was administered at the usual intraoperative time after separation from cardiopulmonary bypass for reversal of heparin. Timed arterial blood samples were obtained after protamine infusion. Blood plasma was subjected to solid-phase extraction and high-performance liquid chromatography. Total (free + heparin-bound) protamine concentration versus time data were subjected to pharmacokinetic modeling. RESULTS: Twenty-six patients completed the study. Total plasma protamine concentrations declined rapidly. Model-independent pharmacokinetic analysis revealed median (range) values as follows: volume of distribution, 5.4 L (0.82 to 34 L); clearance, 1.4 L/min (0.61 to 3.8 L/min); and half-life, 4.5 min (1.9 to 18 min). Schwarz-Bayesian criterion identified a two-compartment exponential model with adjustment for weight in the central compartment volume of distribution as performing better than other compartmental or Michaelis-Menten models. CONCLUSIONS: Protamine has a very short (approximately 5 minutes) half-life after a single 250-mg dose in adult patients. This short half-life could underlie recurrent anticoagulation after initial apparent reversal of heparin.

Aged↗

Ulnar nerve injury and perioperative arm positioning.

Primum non nocere. Hippocrates included this admonition in Epidemics, Book I, Second Constitution, to do good or "to do no harm." However, even the most conscientious health care provider will encounter unexpected and serious adverse medical events. This discussion focuses on one relatively common, often perplexing, and usually unexplained perioperative complication: ulnar neuropathy. Perioperative ulnar neuropathy has received increased scientific attention because it accounts for one third of all nerve injury claims in the American Society of Anesthesiologists (ASA) Closed Claims Study database. In addition, these injuries may result in chronic pain or paresthesia, employment disability, catastrophic economic damages, and malpractice litigation. We will explore the current understanding of perioperative ulnar nerve dysfunction by summarizing the relevant scientific literature and information within the ASA closed-claims database, describing the epidemiologic features of perioperative nerve injuries, discussing relevant clinical investigations and recommendations for safe arm positioning during anesthesia, and reviewing the medico-legal issues inevitably intertwined with this topic, particularly the doctrine of res ipsa loquitur.

Anesthesia↗

Intraoperative insulin therapy does not reduce the need for inotropic or antiarrhythmic therapy after cardiopulmonary bypass.

OBJECTIVE: To determine whether attempted glucose control through intraoperative insulin therapy reduces the need for inotropic or antiarrhythmic therapy after cardiopulmonary bypass (CPB). DESIGN: Post hoc analysis of a randomized, masked clinical trial of insulin therapy for prevention of neurobehavioral deficits. SETTING: Single university hospital. PARTICIPANTS: Nondiabetic patients undergoing elective coronary artery bypass graft surgery (n = 381). INTERVENTIONS: Patients received either insulin infusions in an attempt to maintain blood glucose at 80 to 120 mg/dL (n = 188) or placebo (saline; n = 193). Inotropic therapy was defined as the initiation of vasoactive support with epinephrine or amrinone infusions or mechanical support with the initiation of an intra-aortic balloon pump in the operating room or within 12 hours postoperatively. Antiarrhythmic therapy was defined as cardioversion, antiarrhythmic medications, or pacing. MEASUREMENTS AND MAIN RESULTS: Of patients, 64 in the placebo group and 71 in the insulin group required inotropic support after CPB (p = not significant). The use of cardioversion (55 in placebo group v 61 in insulin group), antiarrhythmic medications (64 in placebo group v 76 in insulin group), and pacing (118 in placebo group v 117 in insulin group) was similar between groups. Inotropic drug support was associated with age >60 years, female gender, reduced preoperative ejection fraction, history of angina, and increased duration of CPB. CONCLUSION: Intraoperative insulin therapy did not reduce the use of inotropic or antiarrhythmic support after cardiac surgery with CPB. The lack of benefit may be due to the inability to prevent hyperglycemia during the physiologic stress of CPB or a tribute to the effectiveness of modern myocardial preservation techniques.

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The pharmacokinetics and cardiovascular effects of a single intravenous dose of protamine in normal volunteers.

UNLABELLED: Despite its long use in clinical medicine, protamine concentrations and pharmacokinetics in humans have not been reported. The occasional reoccurrence of anticoagulation after protamine reversal of heparin led us to hypothesize that protamine plasma concentrations decrease rapidly. We developed a method for the measurement of protamine in plasma. Eighteen fit volunteers gave their consent to receive 0.5 mg/kg protamine sulfate administered IV by an infusion pump over 10 min. Heart rate, mean arterial blood pressure, and cardiac output, all measured noninvasively, were recorded and blood samples obtained during and after protamine infusion. Blood plasma was subjected to solid-phase extraction and high-performance liquid chromatography. The administration of protamine was associated with no significant changes in heart rate, mean arterial blood pressure, or cardiac output. Plasma protamine concentrations decreased rapidly, becoming nondetectable within approximately 20 min. Protamine elimination differed significantly between men and women: men had significantly larger areas under the concentration versus time curve. Model-independent pharmacokinetic analysis revealed median (range) values as follows: volume of distribution at steady state, 12.3 (6.9--63.1) L; clearance, 2.2 (1.1--12.1) L/min; and t1/2, 7.4 (5.9--9.3) min. Concentration versus time plots revealed an atypical pattern inconsistent with usual exponential models. The Schwartz-Bayesian criterion identified a one-compartment Michaelis-Menten model and a two-compartment exponential model with irreversible binding as performing better than conventional one- or two-compartmental exponential models; however, performance errors were large with both Michaelis-Menten and exponential models. All models described rapid decreases in protamine blood concentrations. IMPLICATIONS: We developed a method for measurement of protamine in human blood. In volunteers, protamine concentrations decreased rapidly after administration. The rapid disappearance of protamine from the circulation, as defined by a median half-life of 7.4 min, could contribute to cases of "heparin rebound" after initial adequate reversal of heparin.

Adult↗

Pulmonary artery catheter placement for elective coronary artery bypass grafting: before or after anesthetic induction?

UNLABELLED: Pulmonary arterial catheters (PACs) are often used during and after coronary artery bypass grafting. We hypothesized that placement of a PAC would be faster in anesthetized patients. We further hypothesized that the presence or absence of a PAC during the induction of anesthesia would make no difference in hemodynamics, vasoactive drug use, or IV fluid administration during the induction. Patients (n = 200) undergoing elective coronary artery bypass grafting were assigned to PAC insertion either before or after the induction of anesthesia. Total time for PAC insertion, number of finder needle and venous catheter insertion attempts, incidence of carotid artery puncture, arrhythmias or ST segment changes, arterial blood gas analysis, hemodynamic variables, IV fluids, and vasoactive drugs required during and after the anesthetic induction were recorded. Thirty-two different physicians placed the PACs. PAC placement was faster (10 versus 12 min, P = 0.0003) and required fewer punctures with a finder needle (P = 0.0107) in anesthetized patients. There were no significant differences between groups in hemodynamic values or use of vasoactive or anesthetic drugs or IV fluids during the induction. There were also no significant differences between groups in the incidence of myocardial ischemia, arterial hypoxemia, or hypercarbia. Placement of a PAC before the induction of anesthesia consumes more time and fails to improve hemodynamic stability or lessen vasoactive drug use during the induction of anesthesia. IMPLICATIONS: Insertion of pulmonary artery catheters (PACs) before the induction of anesthesia requires more needle sticks and takes longer than insertion after the induction of anesthesia; moreover, previous PAC insertion has no significant effect on hemodynamics or use of vasoactive drugs or IV fluid associated with the induction of anesthesia.

Aged↗