Cardiopulmonary bypass considerations for pediatric patients on the ketogenic diet.

BACKGROUND: There is a population of children with epilepsy that is refractory to anti-epileptic drugs. The ketogenic diet, a high-fat, low-carbohydrate regimen, is one alternative treatment to decrease seizure activity. Special considerations are required for patients on the ketogenic diet undergoing cardiopulmonary bypass (CPB) to prevent exposure to glucose substrates that could alter ketosis, increasing the risk of recurrent seizures. CASE STUDY: A 2-year-old, 9 kilogram male with a history of infantile spasms with intractable epilepsy, trisomy 21 status post tetralogy of Fallot repair, presented to the cardiac operating room for closure of a residual atrial septal defect. All disciplines of the surgical case minimized the use of carbohydrate-containing and contraindicated medications. Changes to the standard protocol and metabolic monitoring ensured the patient maintained ketosis. DISCUSSION: All disciplines within cardiac surgery need to be cognizant of patients on the ketogenic diet and prepare a modified protocol. Future monitoring considerations include thromboelastography, electroencephalography and continuous glucose measurement. Key areas of focus with this patient population in the cardiac surgical theater are to maintain a multidisciplinary approach, alter the required CPB prime components, address cardiac pharmacological concerns and limit any abnormal hematological occurrences.

Evaluation of the Maquet Neonatal and Pediatric Quadrox I with an integrated arterial line filter during cardiopulmonary bypass.

BACKGROUND: Perfusion equipment has evolved since its introduction into clinical practice more than fifty years ago to include smaller cardiopulmonary bypass (CPB) circuits and components. Perfusionists are now exploring the function of new oxygenators with an integrated arterial line filter (IALF). The purpose of this trial was to examine the Maquet Quadrox-I Neonatal and Pediatric oxygenators with IALF in a clinical setting, with respect to gas transfer, heat exchange co-efficiency (HEC), trans-membrane pressure (TMP) gradient and clinical experience. METHODS: The Maquet Quadrox-I Neonatal oxygenator was used on 30 patients ranging from 2.2-13.1 kg. The Maquet Quadrox-I Pediatric oxygenator was used on 15 patients ranging from 12.7-24.5 kg. Arterial and venous blood gases were taken once the patient was stable on CPB and, subsequently, every 30 minutes afterwards, as per institution protocol. The values for gas transfer rates, HEC and TMP gradient were stratified into three main categories with each oxygenator: normothermia, cooling and re-warming. RESULTS: During all conditions, the gas transfer rate with both oxygenators was efficient. The HEC values showed efficient heat exchanger performance during all conditions with both oxygenators. While maintaining CPB flow within the manufacturer's recommended flow rate for each oxygenator, the TMP gradient range for the Neonatal Quadrox-I was 10-40 mmHg and the Pediatric Quadrox-I was 10-60 mmHg. During the clinical trial, foam was shown to break through the cardiotomy on several occasions when high sucker return was required. CONCLUSION: This new line of oxygenators performed well with regards to gas transfer, HEC and TMP gradient, but there were clinical experiences that did not meet expectations. There were repeated incidences with the venous reservoir which ultimately cast a negative light on the design of this new product from Maquet. In the future, the authors would like to evaluate updated versions of this product from Maquet and any other pediatric perfusion devices that could help the patient in the clinical arena.

A systematic evaluation of the core communication skills expected of a perfusionist.

BACKGROUND: The objective of this systematic evaluation was to identify the sentinel standards necessary to obtain a core level of communication required of a clinical perfusionist during cardiopulmonary bypass (CPB). Once these sentinel standards were identified and a core level of communication was established (via four simulated case scenarios), a team of cardiac healthcare professionals was assembled to interpret both the accuracy of response and the speed of response encountered in each case scenario. METHODS: Four simulated case scenarios were utilized in order to replicate the typical patterns of verbal exchange that occur during surgeries using extracorporeal technology. The simulated case scenarios included CPB interactions associated with preparation, initiation, maintenance, termination and post CPB. For all CPB interactions, two variables were measured: accuracy of the perfusionist's response and speed of the perfusionist's response. The cases took place in a controlled setting within an empty operating room at The Children's Hospital of Philadelphia. Four clinical perfusionists each represented the role of the "perfusionist" in all simulated case scenarios. RESULTS: When analyzing the accuracy and speed of the responses, each clinical perfusionist recorded an average score of 96.3% or higher with all case scenarios. Since the clinical perfusionists who participated in the scenarios were primarily pediatric perfusionists, the scores were best during the pediatric case scenario, 99.3% (Case Scenario #4). The lowest scores were captured during Case Scenario #3 (96.3%) which involved a more intense adult patient scenario. CONCLUSION: The systematic evaluation of both response accuracy and response time (presented in various adult and pediatric patient case scenarios) can be beneficial within the realm of perfusion education. Students will be introduced to core communication concepts within the clinical realm. This study supports the idea that simulation and evaluation may ease the transition for students from the didactic to clinical realm in terms of communication. Further studies need to be developed in order to define "standard" CPB communication guidelines for perfusion students.

Characterological depressions. Clinical and sleep EEG findings separating 'subaffective dysthymias' from 'character spectrum disorders'.

Early-onset characterological depressions are distinguished from late-onset chronic depressions that complicate the long-term course of unipolar and nonaffective illnesses. In turn, characterological depressions are divisible into at least two subtypes: (1) "Subaffective dysthymias" have even sex distribution, are often complicated by superimposed depressive episodes, rapid eye movement latency is shortened, and they tend to respond to tricyclics of lithium carbonate. In brief, they share many features of primary affective illness. (2) "Character spectrum disorders," by contrast, represent a heterogeneous mixture of personality disorders with inconstant depressive features, are more common in women, are often complicated by alcohol and drug abuse, and outcome tends to be unfavorable.

Differentiation of primary affective illness from situational, symptomatic, and secondary depressions.

Analysis of family history and antidepressant drug response variables of 100 "neurotic" depressives followed up prospectively over three to four years disclosed that primary depressions (unipolar and bipolar) could be distinguished from nonprimary cases by (1) the early occurrence of "pharmacological-hypomania;" (2) family history of bipolar illness; (3) family history for affective disorder in two or three consecutive generations, especially when "loaded." Although each of these variables alone occurred in only one fifth to one third of the primary group, they individually displayed better than 95% specificity for it. Thus, the confidence with which the diagnosis of primary affective illness could be made in the presence of any of these variables ranged from 88% to 100%. These findings argue for considering such nonsymptomatological variables for their potential in strengthening the phenomenologic diagnostic criteria for depressive illness.

The nosological status of neurotic depression: a prospective three- to four-year follow-up examination in light of the primary-secondary and unipolar-bipolar dichotomies.

One hundred patients with "mild" depressive states, variously referred to as "situational," "reactive," or "neurotic," were studied. During a three- to four-year prospective follow-up, 4% had developed bipolar I, 14% bipolar II, and 22% unipolar disorders with predominantly favorable social outcome. Most of the remainder were suffering from nonaffective disorders; in this group, intermittent depressive symptomatology followed a protacted course (paralleling the underlying disorder) with generally unfavorable outcome. Irrespective of diagnostic subtype, a "characterological" component occurring in 24% of the total sample appeared to predict unfavorable prognosis, including three suicides. The diagnostic usage of the concept of neurotic depression may no longer be clinically meaningful, since it lacks sufficient phenomenological characterization and refers to a heterogeneous group of disorders. The data suggest the merits of a biaxial approach to the nosology of depressive disorders whereby phenomenologically based affective diagnoses are qualified as to the presence or absence of character disorder.

Renal involvement in Behçet's syndrome.

A retrospective study of 77 cases of Behçet's syndrome showed that, of the 33 patients in whom urinalysis was done (including three with systemic amyloidosis reported earlier), 17 had pathological results. A prospective study of 51 of these patients uncovered eight additional subjects with urinary abnormalities, bringing the total to 25. The urinary abnormality was, as a rule, discrete, consisting of proteinuria and/or microhematuria. These occurred in some patients persistently, in some intermittently, in some alternatingly, and in some simultaneously. The initial finding was proteinuria in 10 patients, hematuria in 11, and both in 4. Over the years, eight showed only hematuria, seven only proteinuria and ten, both. The urinary sediment contained neither leukocytes nor casts. Pyelographies were unrevealing when performed and rectal biopsies uncovered no new instance of amyloidosis. These data suggest that a benign renal lesion occurs in Behçet's syndrome, whose pathological substrate, though not yet defined, is not amyloid deposition.

Minoxidil-induced bullous eruption.

A previously unreported side effect--serosanguineous bullae--was found in one patient receiving minoxidil. The eruption disappeared with cessation of the drug and reappeared on rechallenge. The question arises whether continuation of minoxidil treatment could have led to vasculitis.

Carbamazepine neurotoxic reaction after administration of diltiazem.

A patient with epilepsy controlled by carbamazepine developed a carbamazepine neurotoxic reaction after being given an increased dosage of diltiazem hydrochloride as adjunctive therapy. Abrupt withdrawal of diltiazem reduced the circulating carbamazepine concentration and resulted in an epileptic attack. Awareness of the interaction between diltiazem and carbamazepine and careful monitoring of carbamazepine blood levels is recommended to prevent the dangerous neurotoxic effect associated with this combination.

Hypertensive crisis associated with nifedipine withdrawal.

A 71-year-old hypertensive patient experienced a severe hypertensive crisis. His blood pressure was 300/200 mm Hg three days after nifedipine therapy was discontinued. He had been taking nifedipine together with methyldopa. During five months on the combined treatment, his blood pressure had not risen higher than 170/100 mm Hg. A severe hypertensive crisis following abrupt nifedipine withdrawal has not been previously reported, to our knowledge. We recommend that caution be used when abrupt cessation of nifedipine therapy is considered in the treatment of hypertension.

Left ventricular mass in diabetes-hypertension.

BACKGROUND: This study was undertaken to identify whether diabetes mellitus (DM) accelerates the development of left ventricular hypertrophy (LVH) in hypertensive patients. METHODS: Cardiac structure, systolic function, and hemodynamics were evaluated by two-dimensional M-mode echocardiography in diabetic and nondiabetic patients with essential hypertension. RESULTS: Patients with hypertension with and without DM had the same end-systolic and end-diastolic dimensions, cardiac output, total peripheral resistance, and ejection fraction. Diabetic hypertensive patients had greater interventricular septum (1.32 +/- 0.20 vs 1.07 +/- 0.20 cm) and posterior wall (1.20 +/- 0.20 vs 1.00 +/- 0.10 cm) thickness than did nondiabetic hypertensive patients. Consequently, left ventricular mass index was greater in patients with hypertension and DM than in those without DM (158 +/- 45 vs 113 +/- 20 g/m2). With the use of Devereux criteria for recognition of LVH (left ventricular mass index above 134 g/m2 in men and above 110 g/m2 in women), 72% of the diabetic patients had LVH, whereas only 32% of the nondiabetic patients had LVH. Left ventricular contractility, as reflected by the ratio of end-systolic wall stress to end-systolic volume index, was decreased in diabetic compared with nondiabetic hypertensive patients. CONCLUSIONS: The data suggest that DM accelerates the development of LVH in patients with essential hypertension independent of arterial pressure and, therefore, may contribute to the increased cardiovascular morbidity and mortality in patients with hypertension.

Familial hyperpotassemia and hypertension accompanied by normal plasma aldosterone levels: possible hereditary cell membrane defect.

Hypertension and hyperpotassemia that were accompanied by normal plasma aldosterone and low renin levels and were responsive to chlorothiazide administration were found in a 29-year-old patient and two decades later in his 21-year-old son. Their renal function is normal, including response to sodium sulfate, mannitol, and aldosterone infusions. Adrenal insufficiency was excluded. The renin-aldosterone system was proved intact by physiological and pharmacologic stress and angiotensin-II infusion. Also normal were values for blood counts, blood volumes, and erythrocyte and exchangeable body potassium. The postulation of a defective cell membrane impeding potassium influx is supported by the failure of glucose and insulin infusions to substantially reduce hyperpotassemia. In the context of a hereditary disorder (the pedigree, compatible with autosomal dominant inheritance, includes five affected in two generations), hypertension is a second phenotypic character of a single defective pleiotropic gene although its pathogenesis remains unclear.

Clinical use of captopril in Takayasu's disease.

Three patients with Takayasu's disease (TD), initially observed with hypertension and/or congestive heart failure, were treated with captopril, an orally active inhibitor of converting enzyme. As arteritis in this disease is diffuse and extensive, surgical correction of renovascular hypertension is often delayed or impossible. Our experience enables us to recommend captopril for conservative treatment in TD.

Changes in plasma noradrenaline concentration following sympathetic stimulation by gradual tilting.

Plasma noradrenaline concentration was determined by a radioenzymatic method in 10 normal individuals who were subjected to a stepwise tilt through 45 degrees. A gradual increase in noradrenaline was observed with maximal values occurring in most subjects following the full 45 degrees of tilt. Maximal levels were sustained for up to 30 min. In two subjects who fainted, the syncopal episode followed an initial sympathetic postural response as shown by a rise in plasma noradrenaline. For the remaining subjects a significant correlation was found between changes in plasma noradrenaline and mean arterial pressure.

Contribution of nitric oxide to the beneficial effects of enalapril in the fructose-induced hyperinsulinemic rat.

We examined accumulating evidence of the positive contribution of nitric oxide to the pharmacological effects of converting enzyme inhibitors in 36 rats rendered hypertensive, hyperinsulinemic, and hypertriglyceridemic by a fructose-enriched diet. We studied the response of blood pressure, insulin, and triglyceride levels to inhibition of either converting enzyme-kininase II, nitric oxide synthase, or both. Two weeks of the converting enzyme inhibitor enalapril (20 mg/kg) reduced blood pressure from 137 +/- 2 to 105 +/- 7 mm Hg, insulin from 7.6 +/- 2.0 to 2.2 +/- 1.1 pg/mL, and triglycerides from 292 +/- 37 to 163 +/- 37 mg/dL. Treatment with NG-nitro-L-arginine methyl ester (100 mg/kg) raised blood pressure from 144 +/- 7 to 170 +/- 8 mm Hg without affecting the other parameters. Two weeks of concomitant treatment with both agents blunted the hypotensive and beneficial metabolic effects of enalapril; thus, final blood pressure (141 +/- 7 mm Hg), insulin (6.4 +/- 2.4 pg/mL), and triglyceride (231 +/- 51 mg/dL) values were no different from those of untreated fructose-fed rats. These data suggest that persistent synthesis of nitric oxide contributes to the vasodilator and metabolic effects of enalapril in the fructose-fed rat model.

Effects of enalapril, losartan, and verapamil on blood pressure and glucose metabolism in the Cohen-Rosenthal diabetic hypertensive rat.

We undertook the present study to examine the effect of the angiotensin-converting enzyme inhibitor enalapril, the angiotensin II antagonist losartan, and calcium antagonist verapamil on systolic pressure and spontaneous blood glucose levels in rats from the Cohen-Rosenthal diabetic hypertensive strain. Genetic hypertension and diabetes developed in this strain after crossbreeding of Cohen diabetic and spontaneously hypertensive rats. The new rat strain was fed their usual copper-poor sucrose diet, which is essential for the development of this model, and for 4 weeks received either enalapril, losartan, or verapamil. Systolic pressure was reduced significantly compared with controls in all treated groups. Chronic treatment with enalapril or verapamil, but not with losartan, succeeded in lowering spontaneous blood glucose, indicating improved diabetic control. Data suggest that angiotensin-converting enzyme inhibition by enalapril, but not angiotensin II antagonism by losartan, can improve glucose metabolism in addition to its hypotensive effect in a genetic diabetic hypertensive rat strain. This confirms that the drop in glucose with converting enzyme inhibition is highly dependent on bradykinin accumulation. Data further suggest that calcium channel blockade by verapamil can also improve glucose metabolism. The question remains whether the reduction in glucose by verapamil was a result of inhibition of glucogenesis.

Membrane ion transport in Bartter's syndrome: evidence for a new syndrome subtype.

Fifteen patients with Bartter's syndrome (hyponatremic hypochloremic hypokalemic metabolic alkalosis) were compared with 15 healthy volunteers. Red blood cell Na+/H+ and Cl-/HCO3- exchanges were enhanced in all patients with Bartter's syndrome. In calciuric normomagnesemic patients, sensitive to nonsteroidal anti-inflammatory drugs (classic Bartter's syndrome), red blood cell Na+,K+,2Cl- cotransport was markedly reduced, calcium-dependent K+ permeability was moderately increased, and up to 60% of sodium permeability was represented by cAMP-activated fraction (presumably human analog of beta-isoform of Na+/H+ exchange). In noncalciuric hypomagnesemic patients insensitive to indomethacin (Gitelman's syndrome), Na+,K+,2Cl- cotransport was enhanced, Na+ permeability was increased due to calmodulin-dependent fraction, and calcium-dependent K+ permeability was markedly enhanced. A new subtype of Bartter-like syndrome ("variant Bartter's syndrome") has been described in which calciuria, hypomagnesemia, and insensitivity to nonsteroidal anti-inflammatory drugs were associated with decreased Na+,K+,2Cl- cotransport, enhanced calmodulin-activated fraction of Na+ influx, and reduced calcium-dependent K+ permeability.

Effects of doxepin on withdrawal symptoms in smoking cessation.

In a double-blind study, 15 cigarette smokers self-monitored 10 withdrawal symptoms. For the first 21 days (baseline), subjects received doxepin hydrochloride, up to 150 mg/day, or inert medication while continuing to smoke. On day 22, they were instructed to stop smoking; medication was continued. Withdrawal symptoms on the first 28 days of treatment (baseline and 7 days of attempted cessation) were analyzed. During cessation, subjects taking doxepin reported significantly less craving for cigarettes. Results from this study and others suggest that antidepressants may attenuate the severity of symptoms during withdrawal from addictive substances.

Doxepin as an adjunct to smoking cessation: a double-blind pilot study.

In a double-blind study, 19 adults received bedtime doses of either 150 mg of doxepin hydrochloride (N = 9) or placebo (N = 10). After 3 weeks the subjects were instructed to stop smoking and continue taking medication for 4 additional weeks. Cessation was reported by all nine doxepin subjects 1 week after cessation and by seven doxepin subjects 9 weeks after cessation. One placebo subject reported cessation. Cotinine assays generally confirmed cessation but were subject to interpretation. Doxepin assays suggested that the precessation level was associated with cessation. Further studies with larger samples and extended follow-up are needed to determine the reliability of these results.

The effect of chlorthalidone on serum lipids and lipoproteins.

The effect of chlorthalidone treatment on serum lipids and lipoproteins was investigated in 21 hypertensive patients. Chlorthalidone caused an increase in total serum and low density lipoprotein (LDL) cholesterol, but not in high density lipoprotein (HDL) cholesterol. Serum and lipoprotein triglycerides also increased. Our findings suggest that chlorthalidone increases serum concentrations of "atherogenic" lipoproteins (LDL and VLDL), and possibly decreases the levels of a "beneficial" lipoprotein, namely HDL. Thus, the use of this medication may increase a major atherosclerosis risk factor.