Michael H. Hines

Cavernous sinus thrombosis complicating sinusitis.

Background Septic cavernous sinus thrombosis is a rare complication of paranasal sinusitis. Objective To familiarize the clinician with the pathogenesis, diagnosis, and appropriate management of septic cavernous sinus thrombosis. Design Case report and literature review. Setting Pediatric intensive care unit in a university hospital. Patient We present a 12-yr-old female with a 1 wk history of an upper respiratory tract infection with worsening dyspnea, cough, and swelling of the left eye progressing to adult respiratory distress syndrome. Secondary to the need for significant mechanical ventilatory support, venovenous extracorporeal membrane oxygenation was initiated. Computed tomography scan of the head and neck with contrast revealed bilateral cavernous sinus thrombosis. After broad-spectrum intravenous antibiotics and aggressive supportive care in conjunction with surgical intervention (maxillary sinus lavage and right orbital exploration) and anticoagulation therapy, the patient recovered. Blood cultures were positive for Viridans streptococcus. At discharge 3 wks later, the patient had improved, but had right-eye blindness. Conclusions The diagnosis of septic cavernous sinus thrombosis requires a high index of suspicion and confirmation by imaging; early diagnosis and surgical drainage of the underlying primary source of infection in conjunction with long-term intravenous antibiotic therapy are critical for an optimal clinical outcome.

The Pharmacokinetics of ε-aminocaproic Acid in Children Undergoing Surgical Repair of Congenital Heart Defects

&egr;-Aminocaproic acid (&egr;ACA) is often administered to children undergoing cardiac surgery by using empiric dosing techniques. We hypothesized that children would have different pharmacokinetic variables and require a dosing scheme different from adults to maintain stable and effective serum &egr;ACA concentrations. Eight patients were enrolled in our study. &egr;ACA 50 mg/kg was administered three times IV: before, during, and after cardiopulmonary bypass (CPB). Nine serum samples were obtained. &egr;ACA plasma concentrations were measured by using high-performance liquid chromatography, and pharmacokinetic modeling was done by using NONMEM. The best fit was seen with a two-compartment model with volume of distribution (V1) adjusted for weight and CPB. Compared with published results in adults, modeling suggests that weight-adjusted V1 is larger in children than in adults before, during, and after CPB. Clearance from the central compartment (k10) was also greater in children than adults, and declined during CPB. Redistribution rates from the central compartment, k12 and k21, were greater in children and not affected by CPB. We modeled several different dosing regimens for &egr;ACA based on the larger V1, and higher redistribution and clearance variables. We conclude that, because of the developmental differences in pharmacokinetic variables of &egr;ACA, when compared with adult patients, a larger initial dose and faster infusion rate as well as an addi-tional dose on CPB are needed to maintain similar concentrations.

Lessons Learned from a Single Center's Experience with 134 Donation after Cardiac Death Donor Kidney Transplants

BACKGROUND Reports of kidney transplantation from donation after cardiac death (DCD) donors describe high rates of delayed graft function (DGF). STUDY DESIGN From April 1, 2003 to October 17, 2010, we performed 134 kidney transplants from DCD donors including 120 (90%) from standard-criteria donors (SCDs) and 14 (10%) from expanded-criteria donors (ECDs). Nineteen kidneys were recovered from donors managed with extracorporeal interval support for organ retrieval (EISOR) after cardiac arrest to minimize ischemic injury. RESULTS Comparison of donor and recipient characteristics found no differences for cases managed with or without EISOR. Overall actuarial patient survival rates were 93%, 91%, and 89% at 1, 3, and 5 years, respectively, with a mean follow-up of 31 months. Overall actuarial kidney graft survival rates were 89%, 76%, and 76% at 1, 3, and 5 years, respectively. Actuarial graft survival rates of DCD ECD kidneys were 58% and 48% at 1 and 3 years, compared with 90% and 79% at 1 and 3 years for non-ECD grafts (p = 0.013). DGF occurred in 73 patients (54%) overall and was reduced from 55% to 21% (p = 0.016) with the use of EISOR in locally recovered kidneys. The mean resistance value on machine perfusion and the mean estimated glomerular filtration rate 1 month after transplantation were both improved (p < 0.05) in kidneys from donors managed with EISOR. Mean initial hospital stay was reduced from 8.0 to 5.0 days in patients receiving kidneys recovered with EISOR (p = 0.04). CONCLUSIONS EISOR is associated with a lower rate of DGF, lower graft resistance on machine perfusion, and shorter initial hospitalization. Kidneys from DCD SCDs have excellent medium-term outcomes and represent an important means of expanding the donor pool. Kidneys from DCD ECDs have inferior outcomes.

Dobutamine antagonizes epinephrine's biochemical and cardiotonic effects: Results of an in vitro model using human lymphocytes and a clinical study in patients recovering from cardiac surgery

Background Patients may receive more than one positive inotropic drug to improve myocardial function and cardiac output, with the assumption that the effects of two drugs are additive. The authors hypothesized that combinations of dobutamine and epinephrine would produce additive biochemical and hemodynamic effects. Methods The study was performed in two parts. Phase 1 used human lymphocytes in an in vitro model of cyclic adenosine monophosphate (cAMP) generation in response to dobutamine (10‐8 to 10‐4 M) or epinephrine (10‐9 M to 10‐5 M), and dobutamine and epinephrine together. Phase 2 was a clinical study in patients after aortocoronary artery bypass in which isobolographic analysis compared the cardiotonic effects of dobutamine (1.25, 2.5, or 5 [micro sign]g [middle dot] kg‐1 [middle dot] min‐1) or epinephrine (10, 20, or 40 ng [middle dot] kg‐1 [middle dot] min‐1), alone or in combination. Results In phase 1, dobutamine increased cAMP production 41%, whereas epinephrine increased cAMP concentration [almost equal to] 200%. However, when epinephrine (10‐6 M) and dobutamine were combined, dobutamine reduced cAMP production at concentrations between 10‐6 to 10‐4 M (P = 0.001). In patients, 1.25 to 5 [micro sing]g [middle dot] kg‐1 [middle dot] min‐1 dobutamine increased the cardiac index (CI) 15–28%. Epinephrine also increased the CI with each increase in dose. However, combining epinephrine with the two larger doses of dobutamine (2.5 and 5 [micro sign]g [middle dot] kg‐1 [middle dot] min‐1) did not increase the CI beyond that achieved with epinephrine and the lowest dose of dobutamine (1.25 [micro sign]g [middle dot] kg‐1 [middle dot]‐1 min (‐1)). In addition, the isobolographic analysis for equieffective concentrations of dobutamine and epinephrine suggests subadditive effects. Conclusions Dobutamine inhibits epinephrine‐induced production of cAMP in human lymphocytes and appears to be subadditive by clinical and isobolographic analyses of the cardiotonic effects. These findings suggest that combinations of dobutamine and epinephrine may be less than additive.

Hemophagocytic Lymphohistiocytosis Complicating Influenza A Infection

During the influenza A (H3N2) season of 2003–2004, several influenza-related complications and deaths were reported in children. Hemophagocytic lymphohistiocytosis complicating influenza A infection is very rare. We report a 3-year-old girl who presented with severe pneumonia and hemophagocytic lymphohistiocytosis associated with influenza A infection. Clinicians should be aware of hemophagocytic syndrome as a serious complication of influenza A infection.

Late Follow-Up After Thoracoscopic Ductal Ligation

Interventional catheterization and minimally invasive surgical techniques offer the real possibility of a reduction in cost and morbidity when compared with the traditional surgical approach to patent ductus arteriosus. Video-assisted thoracoscopic surgery may prove to be a superior technique because of its application to a wider range of patients needing ductal closure, a lower incidence of residual shunting, no evidence for recurrent shunting, and the absence of intravascular foreign bodies.

Successful kidney transplantation from a donation after cardiac death donor with acute renal failure and bowel infarction using extracorporeal support

As a result of the ever widening disparity between organ supply and demand, a resurgence of interest has occurred in kidney recovery from donation after cardiac death (DCD) donors. New techniques of in situ extracorporeal support offer the potential to reduce warm ischemic injury and optimize donor management prior to organ recovery. In addition, preliminary outcomes using kidneys from selected deceased donors with rising serum creatinine levels have been promising. However, contraindications to successful organ donation and transplantation may include the presence of abdominal compartment syndrome, generalized bowel infarction, refractory shock with profound metabolic and lactic acidosis, and acute anuric renal failure, particularly in the setting of DCD. We report herein the successful recovery and transplantation of kidneys from an unstable donor with the above constellation of conditions in the setting of extracorporeal support after declaration of death by asystole.

Vasomotor instability in neonates with chromosome 22q11 deletion syndrome

Approximately 70% of individuals with chromosome 22q11 deletion syndrome (22q11DS) have congenital heart defects. A host of other vascular problems in these patients, such as tortuous carotid arteries, Raynauds phenomenon, unexplained hypotension, hypertension, and hypothermia, raise the possibility that there may be abnormal autonomic regulation of the vascular system. So far, however, there has been no formal report of autonomic dysfunction in patients with 22q11 deletion. We present two infants with 22q11DS, who had profound hypotension after uncomplicated surgeries for congenital heart disease. The hypotension was not responsive to vasopressor treatment (and extracorporeal membrane oxygenation in one infant) and resulted in death, due to multiorgan system failure. Obvious causes, such as poor cardiac contractility, prolonged circulatory arrest, neurological abnormality, sepsis and blood loss were excluded. On autopsy, no abnormalities were found that could explain the hypotension. We hypothesize that these infants died of severe hypotension due to abnormal vascular tone and that this is a variable feature in individuals with 22q11 deletion. The autonomic nervous system, which is responsible for the regulation of vasomotor tone, may be variably affected in 22q11DS. This could have implications for the surgical management of patients with 22q11DS. Further studies on this topic would establish or refute the association between 22q11DS and dysautonomia.© 2003 Wiley‐Liss, Inc.

Comparison of a prototype esophageal oximetry probe with two conventional digital pulse oximetry monitors in aortocoronary bypass patients

Objective.Pulse oximetry (SpO2) is the noninvasivestandard for monitoring arterial oxygen saturation in patients undergoinganesthesia, but is subject to external interference by motion artifact,peripheral vasoconstriction, and low cardiac output. We hypothesized thatoximetry signals could be acquired from the esophagus when peripheral pulseoximetry is unobtainable. Therefore, we tested an esophageal stethoscope whichincorporates transverse oximetry photodetectors and emitters in patientsundergoing coronary bypass surgery. Methods.Immediately afterinduction of general anesthesia in 10 coronary artery bypass (CABG) patients,Criticare and Nellcor digital probes were positioned on the left hand,concurrent with placement of an esophageal SpO2 probe. A computerrecorded 5,910 matched oximetry signals every 15 sec during an average of 2.5hrs. All SpO2 measurements were before, and immediately afternon-pulsatile, hypothermic cardiopulmonary bypass. Data represent thepercentage (median value [range]) of the total monitored time thata SpO2 value was displayed. Results.The Nellcor (99.8%,range 6.5–100%) and Criticare (99.7%, range 36.6–100%) acquiredand displayed saturation signals more frequently (p= 0.003) than theesophageal monitor (75.3%, range 42.1–95.8%). The two standard digitaloximeters had a mean difference of 0.9%, with a standard deviation of thedifferences of 0.9. The esophageal probe had a mean difference of −5.2%and −4.8%, with standard deviation of differences of 8.0 and 7.7(compared to the Nellcor and Criticare monitors, respectively). Asecond-generation prototype shielded from electrocautery interference wastested in an additional 4 patients. The shielded prototype displayed signalsmore frequently (96.7%, range 68.4–100%) than the original esophagealprototype. Conclusions.Digital pulse oximetry failure is common inCABG patients, probably because of marginal cardiac output and peripheralvasoconstriction associated with hypothermia. Our study could not confirm thatesophageal technology, which utilizes the esophagus as a site oftransflectance oximetry, was superior to conventional digital pulse oximetry.

Depression of cardiac function after deep hypothermic circulatory arrest in deeply anesthetized neonatal lambs

Cardiac dysfunction is common after neonatal cardiac operations. Previous in vivo studies in neonatal animal models however, have failed to demonstrate decreased left ventricular function after ischemia and reperfusion. Cardiac dysfunction may have been masked in these studies by increased endogenous catecholamine levels associated with the use of light halothane anesthesia. Currently, neonatal cardiac operations are often performed with deep opiate anesthesia, which suppresses catecholamine surges and may affect functional recovery. We therefore examined the recovery of left ventricular function after ischemia and reperfusion in neonatal lambs anesthetized with high-dose fentanyl citrate (450 micrograms/kg administered intravenously). Seven intact neonatal lambs with open-chest preparation were instrumented with left atrial and left ventricular pressure transducers, left ventricular dimension crystals, and a flow transducer. The lambs were cooled (< 18 degrees C) on cardiopulmonary bypass (22 +/- 6 minutes), exposed to deep hypothermic circulatory arrest (46 +/- 1 minutes), and rewarmed on cardiopulmonary bypass (30 +/- 10 minutes). Catecholamine levels and indexes of left ventricular function were determined before (baseline) and 30, 60, 120, 180, and 240 minutes after termination of cardiopulmonary bypass. Levels of epinephrine, norepinephrine, and dopamine were unchanged from baseline values. Left ventricular contractility (slope of end-systolic pressure-volume relationship) was depressed from baseline value (31.7 +/- 9.3 mm Hg/ml) at 30 minutes (15.7 +/- 6.4 mm Hg/ml) and 240 minutes (22.7 +/- 6.4 mm Hg/ml) but unchanged between 60 and 180 minutes. Left ventricular relaxation (time constant of isovolumic relaxation) was prolonged from baseline value (19.0 +/- 3.0 msec) at 30 minutes (31.4 +/- 10.0 msec) and 240 minutes (22.1 +/- 2.8 msec) but unchanged between 60 and 180 minutes. Afterload (left ventricular end-systolic meridional wall stress) was decreased at 30, 60, and 240 minutes. Indexes of global cardiac function (cardiac output, stroke volume), preload (end-diastolic volume), and left ventricular compliance (elastic constant of end-diastolic pressure-volume relationship) were unchanged from baseline values. In deeply anesthetized neonatal lambs exposed to ischemia and reperfusion, left ventricular contractility, relaxation, and afterload are markedly but transiently depressed early after reperfusion and mildly depressed late after reperfusion.