A dose-determining trial of heparinase-I (Neutralase) for heparin neutralization in coronary artery surgery.

UNLABELLED: Heparinase-I, a specific heparin-degrading enzyme, may represent an alternative to protamine. We explored the dose of heparinase-I for efficacy and safety in patients undergoing coronary artery surgery. At the conclusion of cardiopulmonary bypass, subjects received 5, 7, or 10 microg/kg of open-label heparinase-I instead of protamine. Activated clotting time (ACT) and its difference from a contemporaneous heparin-free sample (DeltaACT) at 3 min before and 3, 6, and 9 min after heparinase-I determined reversal efficacy. After surgery, we recorded hourly chest tube drainage. Systemic and pulmonary arterial blood pressure and cardiac output measurements before and immediately after heparinase-I were used to evaluate hemodynamic safety. Coagulation measurements included anti-factor Xa and anti-factor IIa activities. Forty-nine patients from seven institutions participated: 12 received 5 microg/kg, 21 received 7 microg/kg, 4 received two doses of 7 microg/kg, 8 received 10 microg/kg, and 4 received two doses of 10 microg/kg. Treatment groups did not differ demographically. Median DeltaACT 9 min later was 11, 7, and 4 s for the 5, 7, and 10 microg/kg groups, respectively. No adverse hemodynamic changes occurred with heparinase-I administration. The authors conclude that heparinase-I effectively restored the ACT after cardiopulmonary bypass. This effect appeared to be dose dependent. IMPLICATIONS: Heparinase-I (Neutralase(TM)) successfully restored activated coagulation time with no adverse hemodynamic events in patients undergoing coronary artery surgery with cardiopulmonary bypass in an open-label dose-determining trial.

The clinical onset of heparin is rapid.

This study used the activated clotting time (ACT) to determine the clinical onset of four different doses of heparin after bolus injection into the central circulation. Ten consenting adults (Group A) undergoing coronary artery bypass grafting were given 350 U/kg of bovine lung heparin and had simultaneous duplicate arterial and venous ACT determinations at baseline and at 30, 60, 90, 120, 180, and 600 s after heparin injection. Twenty additional coronary artery bypass grafting patients were alternately assigned to one of two 10-patient groups (B and C), which were given 200 and 300 U/kg of bovine lung heparin, respectively. Group D consisted of 10 abdominal aortic aneurysmectomy patients who received 70 U/kg of bovine lung heparin. In Groups B, C, and D, duplicate ACT measurements were taken from an indwelling arterial catheter at baseline and at 30, 60, 90, 120, 180, and 300 s after completion of a bolus injection of heparin into the central circulation. After a 70 U/kg heparin dose, all patients had significant ACT prolongation within 30 s, and 8 of 10 had effectively achieved their peak anticoagulation response by that time. In all patients receiving 200, 300, and 350 U/kg of heparin, arterial anticoagulation (ACT > 300 s) occurred and in most patients peaked within 30 s after heparin administration (P < 0.05). Arterial and venous ACTs did not differ significantly from each other at any measurement period, but venous ACTs peaked slightly later than arterial ACTs (within 60 s in 9 of 10 patients). When 200 U/kg or more of heparin is administered into the central venous circulation in hemodynamically stable anesthetized patients, peak arterial ACT prolongation occurs within 30 s and peak venous ACT prolongation within 60 s.

Minimally invasive direct coronary artery bypass: anesthetic, monitoring, and pain control considerations.

OBJECTIVE: Minimally invasive direct coronary artery bypass (MIDCAB) provides many anesthetic challenges including monitoring, managing myocardial ischemia, and pain control. The objective was to evaluate the monitoring requirements and the potential benefits of preischemic conditioning and intrathecal morphine sulfate in MIDCAB patients. DESIGN AND SETTING: This review was retrospective and unrandomized and was conducted at Allegheny University Hospitals, Allegheny General, Pittsburgh, PA. PARTICIPANTS: Sixty-four patients with single coronary artery lesions (> 70% obstruction) underwent attempted MIDCAB during a 1-year period between November 1995 and November 1996. Seven patients required conversion to conventional coronary artery bypass grafting (CABG) with cardiopulmonary bypass (CPB) and two patients required extended thoracotomy incisions. This report describes the remaining 55 patients who underwent MIDCAB. INTERVENTIONS: Some of the MIDCAB patients received intrathecal morphine before anesthetic induction. Ischemic preconditioning was assessed in a subset of patients. RESULTS: MIDCAB was performed in 55 of 64 patients. Transesophageal echocardiography (TEE) was used in all patients and a pulmonary artery catheter was used in 43% of patients. Esmolol was used in 25% of patients to reduce motion of the left ventricle (LV) during the left internal mammary artery (LIMA)-LAD anastomosis, but was used less often as the surgeons adapted to the use of a retractor that stabilized the ventricular wall adjacent to the site of the LIMA-LAD anastomosis. LAD occlusion caused reversible, regional systolic dysfunction by TEE in the anterior and apical LV segments. During LAD occlusion, nitroglycerin was used in 61% of patients and phenylephrine in 24%. Ischemic preconditioning did not prevent increases in systemic or pulmonary artery pressures during LAD occlusion. Most (85%) patients were extubated in the operating room. Intrathecal morphine decreased postoperative analgesic requirements. The mean hospital length of stay (LOS) was 4.0 +/- 1.7 days (range, 1 to 10 days). CONCLUSIONS: MIDCAB may reduce hospital LOS for patients with single vessel coronary artery lesions when compared with median sternotomy with a LIMA-LAD graft performed on cardiopulmonary bypass. Pharmacologic heart rate control during the LIMA-LAD anastomosis is not critical with the use of a surgical retractor which diminishes ventricular motion. A single 5-minute test LAD occlusion did not protect against subsequent regional ischemic dysfunction in our subset of patients with normal baseline function.

Intraoperative interstitial radiation therapy for hepatic metastases from colorectal carcinomas.

Liver metastases from colorectal carcinomas occur frequently. While surgical resection offers the only hope for long-term cure, unsuspected bilobar metastases or extrahepatic metastatic disease may be found at laparotomy, precluding hepatic resection for cure. In this setting intraoperative interstitial hepatic irradiation using the Gamma Med II (Mick Radio-Nuclear Instruments, Bronx, New York) remote afterloading irradiator and an Iridium-192 source permits delivery of a tumoricidal dose to liver tumor(s) with a limited radiation dose to adjacent normal liver. Six patients underwent laparotomy for potential resection of hepatic metastases in a shielded operating room equipped with remote anesthesia monitoring capability and were found to be unresectable. An upper hand retractor facilitated liver exposure during the exploratory and subsequent radiation phases of the procedure. Intraoperative interstitial radiation therapy was performed in each patient. No significant complications occurred on follow-up from 2 to 9 months. Hepatic tumor regression or stabilization occurred on sonography and/or CT scan in each case with a median follow-up of 5 months. The technique offers the potential to ablate discrete tumor nodules within the liver. Ongoing clinical trials will determine the role of intraoperative interstitial radiation in the treatment of hepatic metastases.

Intraoperative single-dose radiotherapy. Observations on staging and interstitial treatment of unresectable liver metastases.

Fourteen patients with a history of colonic cancer were evaluated for metastatic disease and were thought to have unresectable disease confined to the liver. Exploratory surgery revealed that two patients had extensive extrahepatic disease, and the procedure was terminated. In 12 patients, closed-end needles (diameter, 2.1 mm) were introduced into each nodule and connected to a 370-MBq (10-Ci) afterloading iridium source. Radiation doses were dependent on nodule size, providing minimum doses of 20 Gy (2000 rad) to the lesion's periphery with rapid radiation falloff avoiding toxic effects to adjacent normal tissue. The maximum number of nodules treated in one patient was 11. The largest nodule treated measured 9 x 6.5 x 6 cm. Cholecystectomy in four patients allowed precise implantation and obviated biliary fistula. Preoperative computed tomography underestimated the number of hepatic metastases in all cases but one, and treatment-induced computed tomographic alterations further limited its utility. Radiation treatment was well tolerated, and the median hospitalization was eight days. Of ten patients whose preoperative carcinoembryonic antigen values exceeded 10 ng/dL, the values in six patients decreased postoperatively.

Crohn's appendicitis in an incarcerated spigelian hernia.

A patient with incarcerated Crohn's appendicitis and a spigelian hernia is presented, representing the challenge in diagnosis, incision choice, and choice of definitive surgical procedure. While it is unlikely that the report of such a patient's course will make prospective recognition of this rare entity more likely, a systematic approach to this patient has allowed a satisfactory result with minimal complications.

Creation of a subcutaneous tunnel for Broviac and Hickman catheters.

The use of the Cordis shunt tunneler has simplified the creation of the subcutaneous tunnel for chronic venous access catheters. The tunneling maneuver is rapid, is associated with little patient discomfort, and in a series of 25 consecutive patients has not been associated with hematoma formation.