Arend E. Meinders

Ectopic fat and insulin resistance: pathophysiology and effect of diet and lifestyle interventions.

The storage of triglyceride (TG) droplets in nonadipose tissues is called ectopic fat storage. Ectopic fat is associated with insulin resistance and type 2 diabetes mellitus (T2DM). Not the triglycerides per se but the accumulation of intermediates of lipid metabolism in organs, such as the liver, skeletal muscle, and heart seem to disrupt metabolic processes and impair organ function. We describe the mechanisms of ectopic fat depositions in the liver, skeletal muscle, and in and around the heart and the consequences for each organs function. In addition, we systematically reviewed the literature for the effects of diet-induced weight loss and exercise on ectopic fat depositions.

Cerebrovascular Reactivity in Comatose Patients Resuscitated From a Cardiac Arrest

BACKGROUND AND PURPOSE Cerebral blood flow after cardiac arrest is reduced during the delayed hypoperfusion phase, while cerebral metabolic rate of oxygen returns to baseline values. Hypocapnia can induce cerebral ischemia in neurosurgical patients who already have reduced cerebral blood flow. The purpose of the present study was to determine whether comatose patients resuscitated from a cardiac arrest have a normal cerebrovascular reactivity to changes in PaCO2 and whether hypocapnia causes cerebral ischemia. METHODS We measured mean flow velocity (MFV) and pulsatility index (PI) in the middle cerebral artery, jugular bulb oxygen saturation (SjbO2), and arterial-jugular lactate difference (AJLD) during normo-, hypo-, and hyperventilation in 10 comatose patients resuscitated from a cardiac arrest. The first measurements were made within 6 hours after cardiac arrest and repeated 6, 12, and 24 hours later. RESULTS During hypoventilation we observed a significant decrease in PI and an increase in MFV and SjbO2. During hyperventilation PI and MFV did not change, but SjbO2 showed a significant decrease. This was accompanied by an increase in AJLD, suggesting cerebral ischemia. In four patients the SjbO2 decreased below the ischemic threshold of 55%. CONCLUSIONS The cerebrovascular reactivity to changes in arterial carbon dioxide tension is preserved in comatose patients resuscitated from a cardiac arrest. Hyperventilation may induce cerebral ischemia in the postresuscitation period.

Diagnosing pulmonary embolism in pregnancy: rationalizing fetal radiation exposure in radiological procedures

In pregnancy, the diagnosis of pulmonary embolism (PE) is problematic. There is doubt as to whether objective diagnostic tests are needed and confusion as to what objective test is the safest with respect to fetal radiation exposure. A recent study has reported a very low (1.8%) prevalence of high-probability ventilation-perfusion (VQ) lung scans in pregnant women suspected of PE [1]. From this study it is apparent that the clinical diagnosis of PE is inaccurate and therefore objective diagnostic tests are mandatory, in order to avoid treatment of women that do not have PE. Currently, helical computerized tomography (CT) and VQ scintigraphy are themost common diagnostic tests used in nonpregnant patients with suspected PE. Physicians are reluctant to perform helical CT in pregnant women because of potential adverse effects of radiation exposure to the fetus. VQ scintigraphy has been assumed to be associated with less radiation exposure than helical CT. To compare the relative amounts of radiation exposure to the fetus, we calculated fetal radiation exposure when singleand multidetector row helical CT and VQ scintigraphy were performed using our local hospital protocols. Further, we compared our data with data of the literature. Since there are no established methods for calculating fetal radiation exposure in diagnostic radiological procedures, we used a pragmatic approach. The amount of radiation absorbed by the fetus was assumed to be equal to that absorbed by the uterus of a non-pregnant woman. Assessment of the uterus dose was achieved by measurement of the computed tomography dose index and the application of organ dose conversion factors [2]. The following CT protocols were used for fetal dose assessment: 120 kV, 250 mAs, slice thickness 3 mm and pitch factor 1.7 for single-detector row helical CT (Philips AVE, Best, the Netherlands) 2 and 120 kV, 85 mAs, slice thickness 16 · 0.5 mm and pitch factor 1.4 for multidetector row helical CT (Toshiba Aquilion 16, Shimoishigami, Otawara-shi, Tochigi, Japan) 3 . The scanned range extends from the dorsal lung sinus to the top of the lung. Since fetal radiation exposure was calculated, physical measures (e.g. abdominal shielding with lead) to reduce radiation exposure were not taken into account. For the perfusion scintigraphy protocol we used 40 MBq of Technetium-labeled albumin aggregates. In our institution, ventilation scintigraphy is performed with Krypton-81 m, which is inhaled for two minutes per image. The RubidiumKrypton generator generates 450–750 MBq per min. Our calculated data of CT radiation exposure were compared with doses in nuclear medicine and doses calculated by the International Commission on Radiological Protection (ICRP) and the National Radiological Protection Board (NRPB) of the UK [3,4]. The calculated dose of radiation absorbed by the fetus for a single-detector row helical CT was 0.026 mSv. An even lower dose (0.013 mSv) was calculated for the multidetector row helical CT. In comparison, the calculated dose of fetal radiation with perfusion scintigraphy was 0.11–0.20 mSv. In comparison with doses given by the ICRP and NRPB (Table 1), our calculated doses of helical CT were low. Our study suggests that performing a helical CT according to our local protocol, whether singleor multidetector row, exposes the fetus to less radiation than perfusion scintigraphy. Our findings are clearly contradictive to the general idea that helical CT is more hazardous to the fetus than perfusion scintigraphy. Regarding the generalizability of our data, it is apparent that our calculated fetal radiation dose for CT is well within the range of that found by others. It has been documented that radiation exposure to the patient for a given radiological procedure can vary considerably between different institutions and even within the same institution. There are several factors that affect radiation dose from CT, e.g. (beam energy, tubecurrent time product, pitch, collimation, patient size and dose reduction options). Each institution should therefore carefully scrutinize its protocol for performing helical CT and define the optimal balance between minimal patient radiation exposure and maximal diagnostic CT image quality. Correspondence: Dr M.V. Huisman, Department of General Internal Medicine, Room C1 R 43, Leiden University Medical Center, PO Box 960

Weight changes in critically ill patients evaluated by fluid balances and impedance measurements

Objective.To study simple, rapid, and predictive methods to determine body weight changes in critically ill patients. Design.Prospective, consecutive sample. Setting.Medical intensive care unit of a university hospital. Patients.Thirty-one consecutive patients. Interventions.Calculated weight changes, using day-to-day and cumulative fluid balances corrected (in two ways) for insensible losses, were compared with the actual weight changes (mattress bascule). Atetrapolar impedance technique measuring resistance was evaluated for estimating weight changes. Measurements and Main Results.No reliable relationship was found between calculated weight changes using fluid balances corrected for insensible loss and the observed weight changes. An intraindividual relationship was found between actual weight changes and changes in resistance measured with the tetrapolar impedance technique in a group of 24 critically ill patients with large weight changes (11.1 ± 6.7 kg). No such intraindividual relationship was found in seven patients with small weight changes (3.1 ± 2.2 kg). In each patient, the dope coefficient of the change in weight and resistance relationship differed; this individual slope coefficient could be an indication for hydration. Conclusions.Calculated fluid balances are not predictive for actual weight changes in critically ill patients. Absolute weight measurements are indispensable. Changes in resistance corre with weight changes in individual patients if weight changes were >3 kg. (Crit Care Med 21:871–877)

Pulmonary artery wedge pressure and extravascular lung water in patients with acute cardiogenic pulmonary edema requiring mechanical ventilation

This study describe the values of pulmonary artery wedge pressure (PAWP) and the extravascular lung water (EVLW) index in patients with acute cardiogenic pulmonary edema who require mechanical ventilation. Ten consecutive patients with acute cardiogenic pulmonary edema who required mechanical ventilation were studied. Cardiac index was determined with thermodilution. Central venous pressure and PAWP were measured with a pulmonary artery catheter. EVLW index was determined with the thermal dye dilution technique, using a commercially available computer system. Measurements were made at regular preset intervals after the initiation of mechanical ventilation. PAWP was normal at baseline (11.6+/-0.9 mm Hg, range 8 to 17) and did not change. EVLW index was elevated at baseline (13.7+/-1.5 ml/ kg) and decreased to a normal value after 24 hours (8.6+/-1.2 ml/kg, p = 0.02). Concomitantly cardiac index increased from 2.61+/-0.24 to 3.61+/-0.14 L/min/m2 (p = 0.05). There was no correlation between PAWP and EVLW index. Fluid balance was +1,221+/-908 ml after 24 hours and there was a weight gain of 0.88+/-1.06 kg after 24 hours. Thus, patients with acute cardiogenic pulmonary edema requiring mechanical ventilation may have a normal PAWP after mechanical ventilation has been initiated. In a hemodynamic unstable situation, these patients may require fluid challenges to improve cardiac output, despite the presence of pulmonary edema. The pulmonary edema, measured as EVLW index, resolves rapidly when cardiac performance improves, despite positive fluid balances and weight gain in the first 24 hours.

Hyponatremia in intracranial disorders

Hyponatremia is a common electrolyte disturbance following intracranial disorders. Hyponatremia is of clinical significance as a rapidly decreasing serum sodium concentration as well as rapid correction of chronic hyponatremia may lead to neurological symptoms. Especially two syndromes leading to hyponatremia in intracranial disorders need to be distinguished, as they resemble each other in many, but not all ways. These are the syndrome of inappropriate ADH secretion (SIADH) and the cerebral salt wasting syndrome (CSW). The syndrome of inappropriate ADH secretion is characterized by water retention, caused by inappropriate release of ADH, leading to dilutional hyponatremia. The cerebral salt wasting syndrome on the other hand, represents primary natriuresis, leading to hypovolemia and sodium deficit. SIADH should be treated by fluid restriction, whereas the treatment of CSW consists of sodium and water administration. However, in the literature there is abundant evidence that hyponatremia in intracranial diseases is mostly caused by CSW. Therefore, treatment with fluid and salt supplementation seems indicated in patients with intracranial disorders who develop hyponatremia and natriuresis.

Prolonged resuscitation efforts for cardiac arrest patients who cannot be resuscitated at the scene: Who is likely to benefit?

STUDY OBJECTIVE To determine who may benefit from prolonged resuscitation efforts after therapy by emergency medical services system (EMS) personnel has failed to restore vital signs. DESIGN Retrospective chart review. TYPE OF PARTICIPANTS Two hundred sixteen consecutive adult patients with out-of-hospital cardiac arrest who were admitted to the emergency department without vital signs. METHODS Identification of prehospital resuscitation data, therapy in the ED, hospital course, and final outcome. RESULTS Thirty-nine patients (18.1%) were resuscitated successfully. The odds ratio of successful resuscitation in the ED for the patients with ventricular fibrillation at the scene versus those with asystole or electromechanical dissociation was 3.4 (95% confidence interval, 1.5, 7.9). All patients with asystole or electromechanical dissociation, either at the scene or in the ED, died (95% confidence interval, 0, 4.3). CONCLUSION Prolonged resuscitation efforts in the ED for patients with asystole or electromechanical dissociation usually are futile after previous efforts by the EMS personnel have failed to restore vital signs. Transportation to the hospital may not be indicated. However, for patients with persistent ventricular fibrillation, transport is indicated.

Cerebral Blood Flow after Cardiac Arrest

Patients resuscitated from a cardiac arrest have a high (in-hospital) mortality rate between 50–90 %. Although in the past few decades more patients have a return of spontaneous circulation (ROSC), overall prognosis has not substantially improved [1] and only a minority of patients survive with a favorable neurological recovery [2]. In 1972, Negovsky described the ‘post-resuscitation syndrome’, a constellation of pathophysiological processes occurring after ROSC. In 2008, the International Liaison Committee on Resuscitation (ILCOR) proposed a new term: The post-cardiac arrest syndrome [3]. Growing understanding of the post-cardiac arrest syndrome has contributed to the development of new therapeutic strategies. For example, mild therapeutic hypothermia was effective in improving neurological outcome after cardiac arrest in two randomized controlled trials [4,5]. These results were recently confirmed in a retrospective, multicenter observational study showing that the implementation of mild therapeutic hypothermia in Dutch intensive care units (ICUs) was associated with a 20 % relative reduction in hospital mortality [6].

Hyponatremia due to hypothyroidism: a pure renal mechanism.

Hyponatremia is a common disorder. When hyponatremia is the result of hypothyroidism it can be successfully treated with thyroid hormone substitution. We followed cumulative sodium- and fluid balances of a patient with hyponatremia, resulting from hypothyroidism. We concluded that hyponatremia in hypothyroidism is due to a pure renal mechanism, and cannot be ascribed to inappropriate secretion of antidiuretic hormone.

Immediate and long-term effects of addition of exercise to a 16-week very low calorie diet on low-grade inflammation in obese, insulin-dependent type 2 diabetic patients.

OBJECTIVE To assess the short- and long-term effects of addition of exercise to a very low calorie diet (VLCD) on low-grade inflammation in obese patients with type 2 diabetes mellitus (T2DM). METHODS Twenty seven obese, insulin-dependent T2DM patients followed a 4-month VLCD with (n=13) or without (n=14) exercise and were followed up to 18 months. Anthropometric measurements, metabolic and inflammatory parameters were assessed before, directly after the intervention and at 6 and 18 months follow-up. The same measurements were performed only once in 56 healthy lean and 56 healthy obese controls. RESULTS At baseline hsCRP, IL10 and IL8 were significantly elevated in obese T2DM compared to lean healthy controls. After 4 months, despite substantial weight loss (-25.4 ± 1.3 kg), neither the VLCD nor VLCD+exercise had an effect on plasma cytokines. At 6 months, in the weight-stabilizing period, measures of low-grade inflammation had decreased substantially and equally in both intervention groups. Despite subsequent weight regain, beneficial effect was sustained up to 18 months in both groups, except for IL1 and hsCRP which had returned to baseline in the VLCD-only group. CONCLUSION Our findings suggest that severe caloric restriction increases cytokine production by adipose tissue macrophages and that the beneficial effects of weight loss become apparent only in the eucaloric state.