Hypophosphataemia after cardiopulmonary bypass – incidence and clinical significance, a South African perspective

Background: Hypophosphataemia is well-known in the intensive care units (ICU), for example, in refeeding syndrome. There is limited research available for hypophosphataemia in the ‘post-cardiac surgery’ population. Objectives: Defining the incidence of hypophosphataemia after cardiopulmonary bypass, in a South African population. Secondary objectives include the clinical implication of hypophosphataemia on duration of mechanical ventilation, ICU stay, and cardioactive drug support; and possible associations between demographic variables, intraoperative variables (including cardioplegic solution), and the postoperative phosphate levels. Methods: This was a single-centre, non-blinded, prospective cohort analytical study at an academic hospital, in patients presenting for open cardiac surgery. Over a one-year period, 101 patients were included. Preoperative variables included all the factors of the EuroSCORE II risk evaluation score. Intraoperative variables recorded were drug and blood product administration, cardioplegic solution and cardiopulmonary bypass-related variables. Postoperatively, serum phosphate levels were taken daily and postoperative care measures, such as duration of cardioactive drug support, mechanical ventilation, and ICU stay, were recorded. Results: The incidence of hypophosphataemia, immediately postoperative, was 12.6% (95% confidence interval [CI] 6.7–21.0%) and peaked on Day 3 at 29.0% (95% CI 20.1–39.4%). New onset hypophosphataemia at any stage during the ICU stay was 52.6% (95% CI 42.1–63.0%). No significant associations between hypophosphataemia and secondary objectives were found. Conclusion: Hypophosphataemia was common with an incidence higher than expected. This did not translate into a clinical effect, as the degree was usually mild (0.66–0.79 mmol/L).G

Cardiovascular Involvement in Thalassemia Major Patients: WEB-THAL® Data Analysis (A Web-Based Multicentric Database).

Prevalence of Left Ventricular Dysfunction (LVD), and Congestive Heart Failure (CHF) have been widely described in Thalassemia Major (TM) patients (pts), according to age, therapy, severity and coexisting diseases. However, so far no data are available in a large population adequately transfused and chelated. To determine the LV involvement in treated TM patients, we studied 524 pts from 5 Thalassemia Centers in Italy (49% males, mean age 30 yrs, range 16 to 56 yrs). In all pts clinical and echocardiographic data were recorded in WEBTHAL® database, a large co-operative Italian project among Thalassemia Centres based on an Internet-shared software for thalassemia. Data were evaluated blind by two independent researchers. Patients were considered having LVD if at least one cardioactive drug and/or history of cardiopathy (heart failure and/or clinically relevant arrhythmias) was recorded in their file (102/524 patients, 19,5%). Tables I and II summarize the echocardiographic results and cardiological treatment. Table I TM population without LV involvement (n°422 pts) and on cardiological treatment (n° 102 pts) Mean * Statistically significant between groups Pretrasfusional Hb (g/dl) 9,4 Ferritin (μg/dl) mean of last 10yrs 2027,7 LV end diastolic diameter index (mm/m2) 31,8 FS (%) 35,0 EF (%) 60,6 Duration of transfusion period (yrs) 24,5 Pretransfusional Hb (g/dl) 9,5 Ferritin (μg/dl) mean of last 10yrs * 2389,6 LV end diastolic diameter index (mm/m2)* 32,9 FS %* 31,3 EF % 54,4 Duration of transfusion period (yrs)* 26,2 Table 2 Cardiovascular Drugs N° % At least one drug 102 19,5 ACE Inhibitors 81 15,5 Diuretics 39 7,4 Beta-blockers 24 4,6 Antiarrhythmics 16 3,1 Digoxin 8 1,5 The majority of patients (422 subjects, 80.5%) did not take any cardioactive drugs and were considered without LV involvement. Systolic Pulmonary pressure was elevated (PH) (> 25 mmHg) in 10% of pts. ACE-inhibitors were the most used cardiovascular drug (15.5% of the pts), mainly males (n°56 pts, p<0.001). Pts on cardiological treatment showed lower FS%, compared to pts without cardioactive treatment (p< 0.001) and higher LV End Diastolic Diameter Index (32,9 vs 31,2, p< 0.009). Pts with LV involvement had a significatively longer regular trasfusional period compared to patients of matched age and they higher mean ferritin values (Tab1). Female patients had a significantly lower prevalence of LV involvement. In this group EF% and FS% were higher than in males (p< 0,001 and p<0,04, respectively). According to these data, LV involvement is characterized by a large and hypokinetic LV and occurs in 19% of a regularly transfused and chelated TM population. The LV disfunction is likely related to a long exposure to iron load in the heart. The mean values of clinical and echocardiographical variables of TM population without LV involvement can be considered as reference values (Table I).

Organic Reactivity Control by Means of Neighboring Groups and Organometallics. A Personal Account

This review summarizes the main topics of our research and covers the period of the last 15 years. The prime interest is focused on various ways of controlling the regio- and stereoselectivity of selected organic reactions, in particular electrophilic additions, cleavage of cyclopropane rings, and allylic substitutions by means of neighboring groups and/or transition and non-transition metals. In the first part, the factors governing the course of electrophilic additions are assessed, culminating in the formulation of selection rules for the reactivity of cyclohexene systems, and in a concise synthesis of the natural cardioactive drug, strophanthidin. These studies also contribute to a better understanding of the mechanisms of electrophilic additions. The second part describes recent developments in the stereo- and regiocontrolled cleavage of cyclopropane rings by non-transition metals (Tl and Hg), and the reactivity and transmetalation (with Pd) of the primary products. This methodology has resulted in novel routes to unique polycyclic structures, and will have synthetic applications in the near future. Evidence for the stereospecific "corner" cleavage of the cyclopropane ring has been provided for the first time for Tl and later for Hg. The third part deals with transition metal-catalyzed allylic substitution. Evidence for a new "syn" mechanism for the formation of the intermediate (π-allyl)palladium complex has been provided, which runs counter to the generally accepted "anti" mechanism. A novel method for a Pd-catalyzed allylic oxidation has been developed and employed in the synthesis of natural sesquiterpenes. The increasing importance of transition and non-transition metals for synthetic organic chemistry is demonstrated by their unique reactivity in a number of the papers included in this review.

Tocainide: A Severe Adverse Reaction

Tocainide is a primary analog of lidocaine with antiarrhythmic properties used to treat ventricular rhythm disorders. A 76-year-old man with benign paroxysmal premature ventricular contractions was treated with tocainide and developed a generalized maculopapular lupoid eruption, bleeding from the lips and gingivae, vertigo, gross tremors of the extremities, fever, and short-term memory loss, which required hospitalization. The patient recovered slowly over three months with no permanent sequelae after discontinuing the drug and receiving rigorous supportive care. His excellent physical status and absence of concomitant illness contributed to an uneventful recovery. Tocainide is a potent cardioactive drug with a long biological half-life and should be used with caution.

Specific serum quinidine assay by high-performance liquid chromatography.

The cardioactive drug quinidine has a narrow therapeutic index; consequently, determination of serum quinidine concentrations can be important. We describe a relatively rapid and specific assay for quinidine in serum by high-performance liquid chromatography. It is suitable for use in patient monitoring or pharmacodynamic studies. Alkalinized serum is extracted with benzene, which is evaporated under nitrogen and reconstituted with methanol; an aliquot is chromatographed. Quinidine is separated from its metabolites and dihydroquinidine (a contaminant in quinidine raw materials). The retention time for quinidine is 4 min 10 s, for dihydroquinidine it is 5.5 min. Results for patients' sera by this assay method and the double-extraction method of Cramer and Isaksson [Scand. J. Clin. Lab. Invest. 15, 553 (1963] correlate well (r = .975).