Marc Leeman

Serial lactate determinations during circulatory shock.

The time course of lactacidemia was studied prospectively in 17 patients during fluid resuscitation for an episode of noncardiogenic shock, in 5 patients after grand mal seizures, and in 5 patients after successful CPR for cardiac arrest. The 9 patients in whom shock was reversed with fluid administration demonstrated a regular decrease in lactate concentrations, which exceeded 5% of the initial value during the first 60 min of treatment. In the other patients who expired despite similar therapy, lactacidemia was not significantly affected. During circulatory shock, repeated lactate determinations represent a more reliable prognostic index than an initial value taken alone. Changes in lactate concentration can provide an early and objective evaluation of the patients response to therapy.

Erythropoietin response is blunted in critically ill patients

Objectives: Critically ill patients often develop anaemia which can be related to a number of factors. However, the exact causes of anaemia in many patients remain unexplained. We hypothesized that the relationship between erythropoietin (EPO) and haematocrit may be altered in critically ill patients. Design: Serum concentrations of EPO were serially determined by the ELISA method in 36 critically ill, non-hypoxaemic patients who stayed more than 7 days in the Intensive Care Unit, including 22 patients with sepsis and 14 without. Eighteen ambulatory patients with iron-deficiency anaemia served as a control group. Setting: Two University Hospital Intensive Care Departments. Results: A significant inverse correlation between serum EPO and haematocrit levels was found in the control patients (r = −0.81, p < 0.001), but not in the critically ill patients (r = −0.09, NS), except in a subgroup of non-septic patients without renal failure (r = −0.61, p < 0.01). Conclusions: EPO levels can be inappropriately low in critically ill patients, so that EPO deficiency may contribute to the development of anaemia in these patients. This phenomenon is observed not only in the presence of acute renal failure, but also in the presence of sepsis.

Albumin administration improves organ function in critically ill hypoalbuminemic patients: A prospective, randomized, controlled, pilot study*

Objective:To test the hypothesis that administration of albumin to correct hypoalbuminemia might have beneficial effects on organ function in a mixed population of critically ill patients. Design:Prospective, controlled, randomized study. Setting:Thirty-one-bed, mixed medicosurgical department of intensive care. Patients:All adult patients with a serum albumin concentration ≤30 g/L were assessed for eligibility. Principal exclusion criteria were expected length of stay <72 hrs, life expectancy <3 months or a do-not-resuscitate order, albumin administration in the preceding 24 hrs, or evidence of fluid overload. Interventions:The 100 patients were randomized to receive 300 mL of 20% albumin solution on the first day, then 200 mL/day provided their serum albumin concentration was <31 g/dL (albumin group), or to receive no albumin (control group). Measurements and Main Results:The primary outcome was the effect of albumin administration on organ function as assessed by a delta Sequential Organ Failure Assessment score from day 1 to day 7 (or the day of intensive care discharge or death, whichever came first). The two groups of 50 patients were comparable at baseline for age, gender, albumin concentration, and Acute Physiology and Chronic Health Evaluation II score. Albumin concentration did not change over time in the control group but increased consistently in the albumin group (p < .001). Organ function improved more in the albumin than in the control group (p = .026), mainly due to a difference in respiratory, cardiovascular, and central nervous system components of the Sequential Organ Failure Assessment score. Diuretic use was identical in both groups, but mean fluid gain was almost three times higher in the control group (1679 ± 1156 vs. 658 ± 1101 mL, p = .04). Median daily calorie intake was higher in the albumin than in the control group (1122 [935–1158] vs. 760 [571–1077] kcal, p = .05). Conclusions:Albumin administration may improve organ function in hypoalbuminemic critically ill patients. It results in a less positive fluid balance and a better tolerance to enteral feeding.

Self-measured versus ambulatory blood pressure in the diagnosis of hypertension.

Objective We examined to what extent self-measurement of blood pressure at home (HBP) can be an alternative to ambulatory monitoring (ABP) to diagnose white-coat hypertension. Methods In 247 untreated patients, we compared the white-coat effects obtained by HBP and ABP. The thresholds to diagnose hypertension were ⩾ 140/⩾ 90 mmHg for conventional blood pressure (CBP) and ⩾ 135/⩾ 85 mmHg for daytime ABP and HBP. Results Mean systolic/diastolic CBP, HBP and ABP were 155.4/100.0, 143.1/91.5 and 148.1/95.0 mmHg, respectively. The white-coat effect was 5.0/3.5 mmHg larger on HBP compared with ABP (12.3/8.6 versus 7.2/5.0 mmHg; P < 0.001). The correlation coefficients between the white-coat effects based on HBP and ABP were 0.74 systolic and 0.60 diastolic (P < 0.001). With ABP as a reference, the specificity of HBP to detect white-coat hypertension was 88.6%, and the sensitivity was 68.4%. Conclusion Our findings are in line with the recommendations of the ASH Ad Hoc Panel that recommends HBP for screening while ABP has a better prognostic accuracy.

Survey on treatment of hypertension and implementation of World Health Organization/International Society of Hypertension risk stratification in primary care in Belgium

Objective To gain insight into the prevalence, treatment and control of hypertension and into the implementation of the 1999 World Health Organization/International Society of Hypertension guidelines for the management of hypertension in general practice in Belgium. Design A prospective cross-sectional survey. Setting Primary care. Methods Participating physicians enrolled the first 15 men, at least 55 years old, who visited the surgery, measured their blood pressure with a validated automatic device and recorded data on age, medical history, drug utilization, cardiovascular risk factors and target organ damage. Patients were considered to have hypertension when systolic blood pressure was ⩾ 140 mmHg, diastolic blood pressure was ⩾ 90 mmHg or when they were under antihypertensive therapy. Results Among 3761 evaluable patients, 74% were considered to be hypertensive, 80% of whom were treated with antihypertensive drugs. Blood pressure was under control in 38% of the treated patients and in 31% of all hypertensives. Among the 1316 hypertensive patients in whom risk stratification was possible, 47, 56 and 86% of the patients in, respectively, the medium, high and very high risk groups were treated with antihypertensive drugs. Among the treated patients, 46, 37 and 31%, respectively, had reached goal pressure. Within each risk category, patients were treated more frequently when baseline blood pressure was higher. Logistic regression analysis revealed that hypertension grade and level of risk contributed independently to the odds of being treated. Conclusions The results indicate that a large number of older hypertensive men are treated with antihypertensive drugs in primary care, but that the goal blood pressure is not reached in a substantial number of patients due to undertreatment. Furthermore, whereas patients at higher risk are treated more frequently than patients at lower risk, blood pressure itself remains an important factor for the initiation of antihypertensive drug therapy within each risk category.

Validity of pulse pressure and augmentation index as surrogate measures of arterial stiffness during beta-adrenergic stimulation.

Objective Increased arterial stiffness is a determinant of cardiovascular mortality. Pulse wave velocity (PWV) is a direct measure of arterial stiffness. Aortic augmentation index (AI) and pulse pressure (PP) are surrogate measures of arterial stiffness. Both PWV, AI and PP increase with cardiovascular risk factors. The aim of this study was to test the validity of AI and PP as surrogate measures of arterial stiffness compared with PWV, during beta-adrenergic stimulation with Isoprenaline (Iso). Design and methods A total of 41 healthy volunteers entered a randomized, double-blind, placebo-controlled, cross-over study. In random order, subjects were given intravenous infusion in equal volume of Iso 8 μg/kg per min (dissolved in glucose 5%) and placebo (glucose 5%). A wash-out period of 25 min was observed between the infusions. Measurements included blood pressure (BP), heart rate (HR), PWV, and AI. PWV were determined using complior (Complior, Artech-Medical, Paris, France). AI and aortic PP were obtained from pulse wave analysis of radial applanation tonometry, using transfer function (SphygmoCor Windows software). Results Baseline AI increased (P < 0.05) with aging, a lower height and a larger diastolic BP (DBP). Iso increased (P < 0.0001) HR, brachial SBP, brachial and aortic PP as compared with placebo. In contrast, Iso decreased (P < 0.05) AI, brachial DBP, peripheral PWV, but not aortic PWV. Decrease of AI induced by Iso was not related to PWV. In stepwise multiple regression changes in HR, brachial SBP and DBP were independent determinants of AI response to Iso (r = 0.78, P < 0.0001). Conclusions Our findings show that AI and PP fail as surrogate measures of arterial stiffness during beta-adrenergic stimulation.

Ethnic differences in arterial stiffness and wave reflections after cigarette smoking.

Background Smoking increases plasma nicotine. Nicotine releases catecholamines and alters arterial distensibility. The nicotine intake per cigarette is greater and serum cotinine levels, the proximate metabolite of nicotine, are higher in Blacks than in Whites. We tested the hypothesis that cigarette smoking increases the pulse wave velocity (PWV), a marker of arterial stiffness, and the augmentation index (AI), a measure of wave reflection, more in Blacks than in Whites. Methods We matched Black (n = 30) and White (n = 30) smokers for age, gender, body mass index and height. We determined carotid-femoral PWV (PWVCF) and carotid-radial PWV (PWVCR) (Complior), the AI derived from the aortic pressure waveform (applanation tonometry, Sphygmocor), blood pressure, heart rate (HR) and cotinine levels before and after cigarette smoking. We also performed measurements in 16 participants after sham smoking. Results Smoking increased the AI, PWVCF and PWVCR in the whole population (all P < 0.05, n = 60). Increases in the AI and PWV were positively related to serum cotinine levels (all P < 0.05). Smoking increased serum cotinine (P = 0.01) and mean blood pressure (P = 0.03) more, but raised the HR to a lesser extent, in Blacks [+8 ± 4 versus +13 ± 6 beats/min in Whites (mean ± SD), P = 0.01]. Blacks disclosed larger increases in AI adjusted for HR (Blacks, +7.2 ± 8 versus Whites, +4.4 ± 8%; P = 0.03), PWVCF (Blacks, +1.1 ± 0.2 versus Whites, +0.6 ± 0.3 m/s; P < 0.01) and PWVCR (Blacks, +1.4 ± 0.1 versus Whites, +0.7 ± 0.4 m/s; P < 0.01) normalized for the mean blood pressure. No changes were observed with sham smoking. Conclusions Smoking acutely increases the PWV and AI in Blacks more than in Whites. Differences in nicotine metabolism and β-adrenergic sensitivity could explain these findings.

Reappearance of a normal circadian rhythm of blood pressure after cardiac transplantation.

Twenty-four-hour blood pressure (BP) and heart rate profiles were recorded in 19 patients 1 and 7 months after cardiac transplantation using noninvasive ambulatory monitors and were analyzed using the periodogram method. These recordings were compared with those of control subjects matched for age, sex and daytime ambulatory BP. One month after transplantation, the nighttime decrease in systolic and diastolic BPs were attenuated in the patients as compared to the control subjects (p less than 0.001). The daily oral dose of prednisolone was inversely correlated with the magnitude of the nighttime decreases in systolic and diastolic BPs (r = -0.47 and -0.53, p less than 0.05). In contrast, 7 months after transplantation, the nighttime decrease in systolic and diastolic BPs reappeared in the patients and was of similar magnitude as that in the control subjects. When the immunosuppressive regimens during the 2 periods of recordings were compared, the reduction in the daily oral dose of prednisolone administered to the patients 7 months after transplantation was correlated with the observed increase in the day-night systolic and diastolic BP difference (r = 0.61, p less than 0.01 and r = 0.51, p less than 0.05). Thus, data show the reappearance of normal circadian BP profiles in patients with long-term heart transplants, and suggest that glucocorticoid administration may contribute to the abnormal nocturnal BP profiles observed 1 month after transplantation.

Enhancement of Hypoxic Pulmonary Vasoconstriction by Metabolic Acidosis in Dogs

The effects of HCl infusion on multipoint mean pulmonary arterial pressure (PAP)/cardiac index (CI) plots in pentobarbital-anesthetized dogs whose lungs were ventilated alternately in hyperoxia (fraction of inspired O2 [FIO2], 0.4) and hypoxia (FIO2, 0.1) were investigated. Over the range of CI studied (1 to 5 l.min-1.m-2), hypoxia increased PAP in 22 dogs (responders) and did not affect PAP in 16 other dogs (nonresponders). In eight nonresponders, two repetitions of alternated 0.4 and 0.1 FIO2 exposures did not restore hypoxic pulmonary vasoconstriction (HPV), defined as a hypoxia-induced increase in PAP at a given flow. Intravenous infusion of 2 M HCl (2 mmol.kg-1.h-1) decreased arterial pH from normal to around 7.20 in eight responders and eight nonresponders. This metabolic acidosis increased PAP at all levels of CI in hyperoxia and in hypoxia in all the dogs, enhanced HPV in the responders, and restored HPV in the nonresponders. In eight responders, 2 M HCl infusion (2 mmol.kg-1.h-1) together with a 7% sodium bicarbonate infusion (adjusted to maintain arterial pH unchanged) did not affect hyperoxic or hypoxic PAP/CI plots. Pretreatment with 1 g acetylsalicylic acid iv (6 dogs) did not affect the pulmonary vasoreactivity to HCl-induced (2 M HCl, 2 mmol.kg-1.h-1) metabolic acidosis. It was concluded that in intact dogs: 1) metabolic acidosis enhances HPV; 2) at the given dose, HCl does not produce pulmonary vascular effects unrelated to the circulating blood pH; and 3) it is unlikely that the pulmonary vasoreactivity to metabolic acidosis is mediated by products of the cyclooxygenase pathway.

Effects of vasodilators on gas exchange in acute canine embolic pulmonary hypertension.

Pulmonary vascular tone was investigated by the construction of pulmonary arterial pressure (PAP)/cardiac output (Q) plots, and gas exchange, by the multiple inert gas elimination technique, in 24 anesthetized dogs before and after pulmonary embolization of autologous clots. Three PAP/Q plots were obtained by a manipulation of venous return at baseline and 60 min and 110 min after embolization. Before the third PAP/Q plot, the dogs were randomly allocated to one of the following iv treatments: 1) placebo (n = 6); 2) prostaglandin E1 (PGE1) 0.4 microgram.kg-1.min-1 (n = 6); 3) hydralazine 2 mg/kg (n = 6); and 4) nitroprusside 10 microgram.kg-1.min-1 (n = 6). These vasodilators decreased systemic arterial pressure by a mean of 44%. Ventilation-perfusion (VA/Q) distributions were determined at the same Q (2.4 +/- 0.1 l.min-1.m-2, mean +/- SE) of each PAP/Q plot. Embolization increased the intercept and the slope of the PAP/Q plots (P less than 0.001). Distributions of VA/Q were only moderately impaired, with an increased dispersion of both VA and Q and a shift of VA distributions to higher VA/Q. PaO2 changed from 208 +/- 5 to 172 +/- 8 mmHg (P less than 0.01) (fraction of inspired O2 was 0.4). None of the treatments had any effect on VA/Q distributions. Placebo and PGE1 had no effect on PAP/Q plots. Hydralazine and nitroprusside reduced the slope of the PAP/Q plots. Thus, in this canine model of acute pulmonary embolism: 1) VA/Q distributions were moderately impaired accounting for only slight hypoxemia, and 2) pulmonary hypertension was partially reversible by hydralazine and by nitroprusside without associated non-flow-dependent change in VA/Q distributions and arterial oxygenation.