Preclinical readiness testing of the Arrow International CorAide left ventricular assist system

BACKGROUND: Left ventricular assist system technologies are currently being developed as effective alternatives to cardiac transplantation. In this study, in vivo testing of the Arrow International CorAide left ventricular assist system was conducted to determine its preclinical readiness based on demonstrated system performance and biocompatibility. METHODS: Arrow International CorAide blood pump assemblies were implanted in 7 calves for 1-month (n = 4) and 3-month (n = 3) durations without the use of chronic anticoagulation therapy. Hemodynamic performance, physiologic pump control, end-organ function, and device-related adverse events were evaluated during the studies and at autopsy. RESULTS: Hemodynamics were stable in all cases with a mean pump flow of 4.1 +/- 0.8 L/min and a mean arterial pressure of 101 +/- 4 mm Hg. In all calves, renal and hepatic function remained normal with no incidence of hemolysis, infection, bleeding, or embolism. The CorAide physiologic control algorithm demonstrated appropriate pump speed and flow adjustments in response to physiologically induced inputs, and the system's external electronic components demonstrated no hardware or software malfunction. All 7 cases were sacrificed electively. Autopsy revealed no sign of end-organ disease on gross and histologic examinations, and no device failure, malfunction, or mechanical wear of the pump blood-bearing surfaces was found. CONCLUSIONS: The Arrow CorAide left ventricular assist system demonstrated effective pump performance and good biocompatibility with no incidence of device-related adverse events. This system has completed its preclinical readiness testing and is approved for clinical trials in Europe in 2003.     

Sequence-specific DNA strand cleavage by <Superscript>111</Superscript>In-labeled peptide nucleic acids

Peptide nucleic acids (PNAs) bind tightly and sequence-specifically to single- and double-stranded nucleic acids, and are hence of interest in the design of gene-targeted radiotherapeutics that could deliver the radiodamage to designated DNA and/or RNA sites. As a first step towards this goal, we developed a procedure for incorporation of Auger electron-emitting radionuclide (indium-111) into PNA oligomers and studied the efficiency of PNA-directed cleavage of single-stranded DNA targets. Accordingly, diethylene triamine penta-acetic acid (DTPA) was conjugated to the lysine-appended mixed-base PNAs and sequence-homologous DNA oligomer with a proper linker for comparative studies. By chelation of PNA-DTPA and DNA-DTPA conjugates with ¹¹¹In³⁺ in acidic aqueous solutions, ¹¹¹In-labeled PNA and DNA oligomers were obtained. Targeting of single-stranded DNA with PNA-DTPA-[¹¹¹In] conjugates yielded highly localized DNA strand cleavage; the distribution of breaks along the target DNA strand has two maxima corresponding to both termini of PNA oligomer. After 10–14 days, the overall yield of breaks thus generated within the PNA-targeted DNA by ¹¹¹In decay was 5–7% versus 2% in the case of control oligonucleotide DNA-DTPA-[¹¹¹In]. The estimated yield of DNA strand breaks per nuclear decay is ~0.1 for the PNA-directed delivery of ¹¹¹In, which is three times more than for the DNA-directed delivery of this radionuclide. This in vitro study shows that ¹¹¹In-labeled PNAs are much more effective than radiolabeled DNA oligonucleotides for site-specific damaging of DNA targets. Accordingly, we believe that PNA oligomers are promising radionuclide delivery tools for future antisense/antigene radiotherapy trials.     

Sensorimotor anesthesia and hypotension after subarachnoid block: combined spinal-epidural versus single-shot spinal technique

The extent of the intrathecal compartment depends on the balance between cerebrospinal fluid and subatmospheric epidural pressure. Epidural insertion disrupts this relationship, and the full impact of loss-of-resistance on the qualities of subarachnoid block is unknown. In this study we sought to determine if subarachnoid block, induced by combined spinal-epidural (CSE) using loss-of-resistance to air could render higher sensory anesthesia than single-shot spinal (SSS) when an identical mass of intrathecal anesthetic was injected. Sixty patients, scheduled for minor gynecological procedures, were randomly allocated into three groups all receiving 10 mg of 0.5% hyperbaric bupivacaine. In the SSS group, intrathecal administration was through a 27-gauge Whitacre spinal needle inserted at the L3-4 level. For the CSE group, the epidural space was identified with an 18-gauge Tuohy needle using loss-of-resistance to 4 mL of air. After intrathecal administration, a 20-gauge catheter was left in the epidural space. No further drug or saline was administered through the catheter. The procedure was repeated in group CSE ((no-catheter)) except without insertion of a catheter. Sensorimotor anesthesia was assessed at regular 2.5-min intervals until T10 was reached. In all aspects, there was no difference between CSE and CSE ((no-catheter)). Peak sensory level in SSS was lower than CSE and CSE ((no-catheter)) (median T5 [max T3-min T6] versus (T3 [T1-4] and (T3 [T2-5]) (P < 0.01). During the first 10 min postblock, dermatomal thoracic block was the lowest in SSS (P < 0.05). Time for regression of sensory level to T10 was also shortest in SSS. Hypotension, ephedrine use and period of motor recovery were more pronounced in CSE and CSE ((no-catheter)). We conclude that subarachnoid block induced by CSE produces greater sensorimotor anesthesia and prolonged recovery compared with SSS. There is also a more frequent incidence of hypotension and vasoconstrictor use despite using identical doses and baricity of local anesthetic. IMPLICATIONS: This study confirms that induction of subarachnoid block by a combined-spinal epidural technique produces a greater sensorimotor anesthesia and results in prolonged recovery when compared with a single-shot spinal technique. There is a more frequent incidence of hypotension and vasoconstrictor administration despite identical doses of intrathecally administered local anesthetic.     

The safety and efficacy of a fentanyl patient-controlled transdermal system for acute postoperative analgesia: a multicenter, placebo-controlled trial

A noninvasive method of delivery of parenteral opioids for management of acute pain may offer logistic advantages for patients and nursing staff. A patient-controlled transdermal system (PCTS) under development consists of a preprogrammed, self-contained drug-delivery system that uses electrotransport technology (E-TRANS, ALZA Corp, Mountain View, CA) to deliver 40 micro g of fentanyl HCl over 10 min per on-demand dose for patient-controlled analgesia (PCA). In this randomized, double-blinded, placebo-controlled trial we compared the efficacy and safety of on-demand fentanyl HCl PCTS 40 microg against placebo for postoperative pain up to 24 h after major abdominal, orthopedic, or thoracic surgery in 205 patients. The primary efficacy measurement was the percentage of patients withdrawn from the study because of inadequate analgesia after completing at least 3 h of treatment. Secondary efficacy measures included mean pain intensity (using visual analog scales), patient global assessments, and investigator global assessments. Of 189 patients considered evaluable for efficacy, 25% of patients in the fentanyl HCl PCTS 40 microg group withdrew because of inadequate analgesia, compared with 40.4% of the placebo group (P < 0.05). Use of fentanyl HCl PCTS 40 micro g was associated with lower VAS scores and higher mean patient and investigator global assessment scores compared with placebo. No patient experienced clinically relevant respiratory depression. This study showed that a fentanyl HCl PCTS 40 microg for PCA was superior to placebo and well tolerated for the control of moderate to severe postoperative pain for up to 24 h after major surgery. IMPLICATIONS: This multicenter, randomized, double-blinded, placebo-controlled trial showed that an on-demand fentanyl HCl patient-controlled transdermal system (PCTS) was superior to placebo and well tolerated for the control of moderate to severe postoperative pain for up to 24 h after major surgery. This fentanyl HCl PCTS is a preprogrammed, needle free, self-contained drug-delivery system that uses electrotransport technology (iontophoresis) to deliver 40 microg of fentanyl per on-demand dose.     

The infected median sternotomy wound: management with the rectus abdominis musculocutaneous flap

Treatment of patients with infected median sternotomy wounds includes debridement and closure using vascularized tissue, most often the pectoralis major muscle. However, occasionally, surgeons use other flaps to close sternotomy wounds. The purpose of this study is to review 1 center's experience with infected median sternotomy wounds utilizing a less common technique, the rectus abdominis musculocutaneous flap.     

Fluid administration during abdominal surgery influences on coagulation in the postoperative period

OBJECTIVE: Postoperative coagulopathy is an important concern for patients after major surgery. Our objective was to define the factors that correlate with postoperative deterioration in coagulation. DESIGN: Retrospective clinical case study. SETTING: University hospital. PARTICIPANTS: Adult patients (n = 150), who underwent major abdominal surgery, were randomly chosen to participate in the study. For each patient, demographic and medical data, anesthetic information, type and duration of surgery, hemodynamic variables, fluid administration, as well as preoperative and postoperative prothrombin time and partial thromboplastin time were collected. Statistical analysis was used to determine which factors correlated with deterioration of coagulation tests. RESULTS: We found statistically significant correlation between deteriorating coagulation functions and administration of more than 3 l of crystalloids during abdominal surgery. There was also correlation between administration of more than 500 ml of colloid administration and elongation of protrombin time. The remainder of the above studied factors did not correlate with deteriorating coagulation. CONCLUSIONS: Administration of more than 3-l crystalloids or 500-ml colloids during abdominal surgery correlates with postoperative coagulopathy.     

Neurophysiologic monitoring and pharmacologic provocative testing for embolization of spinal cord arteriovenous malformations

BACKGROUND AND PURPOSE: Embolization of a spinal cord arteriovenous malformation (SCAVM) is still considered risky. We evaluated the efficacy and reliability of pharmacologic provocative testing with neurophysiologic monitoring in the embolization of SCAVMs. METHODS: We retrospectively analyzed results of 60 provocative tests during 84 angiographic procedures (in 52 patients) with intended endovascular embolization. Tests included 47 sodium amytal and 56 lidocaine injections. All procedures were performed with general anesthesia and monitoring of cortical somatosensory evoked potentials (SEPs) and transcranial motor evoked potentials (MEPs). For provocative testing, 50 mg of amytal and 40 mg of lidocaine were consecutively injected through a microcatheter placed at the position of intended embolization. If SEPs and MEPs did not change, embolization was performed with N-butyl-cyanoacrylate (NBCA). If SEPs or MEPs changed, NBCA embolization was not performed from that catheter position. RESULTS: One false-negative result occurred, with an increase in spasticity after embolization. Nineteen positive results occurred: four after amytal injection and 15 after lidocaine injections. Seven injections in a posterior spinal artery feeder resulted in loss of SEPs or MEPs. Eleven injections in the anterior spinal artery feeder and one in the posterior inferior cerebellar artery feeder resulted in loss of MEPs. CONCLUSION: Provocative testing with amytal and lidocaine combined with neurophysiologic monitoring had a high negative predictive value and was a useful adjunct for SCAVM embolization. Both amytal and lidocaine should be used as provocative agents, and both SEPs and MEPs should be monitored.