Dopamine versus norepinephrine: is one better?

Dopamine and norepinephrine are widely used as first line agents to correct hypotension in patients with acute circulatory failure. There has been considerable debate in recent years as to whether one is better than the other. Both drugs can increase blood pressure in shock states, although norepinephrine is more powerful. Dopamine can increase cardiac output more than norepinephrine, and in addition to the increase in global blood flow, has the potential advantage of increasing renal and hepatosplanchnic blood flow. However, dopamine has potentially detrimental effects on the release of pituitary hormones and especially prolactin, although the clinical relevance of these effects is unclear. Observational studies have provided conflicting results regarding the effects of these two drugs on outcomes, and results from a recently completed randomized controlled trial are eagerly waited.

90-day follow-up of patients treated with Drotrecogin Alfa (activated) for severe sepsis: a Belgian open label study.

INTRODUCTION: Severe sepsis is the major cause of mortality in intensive care units (ICUs). The BOOST study (= B (Belgian) OO (Open Label) ST (Study)) is a Belgian open-label trial designed to pragmatically assess the safety and efficacy of Drotrecogin Alfa (activated) (DAA), the only registered treatment in this indication with favourable ratio benefit/risk. METHODOLOGY: Adult patients with severe sepsis and 2 or more sepsis-induced organ dysfunctions (OD) within the 48-hour period preceding the treatment (DAA at 24 microg/kg/h for 96 hours), were included between January 2003 and October 2003. Platelet count < 30 000/mm3 and increased risk for bleeding were exclusion criteria. Mortality and location were evaluated at 28 and 90 days. RESULTS: Of the 100 included patients, 97 (median age: 66 years; men/women: 57/40) were treated and completed the study. The predominant infection sites were lung (49%) and abdomen (29%) and 35% had had recent surgery. The mean and median numbers of OD were 3.4 and 3.0, respectively, and most patients (80 %; 77/97) had 3 or more organ failures at baseline, predominantly respiratory (95%) and cardiovascular (87%). The mean APACHE II score was 25.3 (range: 6-53). The 28-day mortality rate was 32.0% (90% CI: 24.2-39.7) and increased with the number of OD: from 15% (1.9-28.1) for2 ODs, to 71% (52.4-88.8) for 5 ODs. At day 28, the 66 surviving patients were located in general ward (35%), in the ICU (32%) or at home (30%). The 90-day mortality rate was 42% (90% CI: 34.0-50.5), with most of the survivors (73%) staying at home. Eight serious adverse events, including 4 bleedings, were reported between study days 2 and 5, in 5 patients (5.2%) and led to death in 2 patients (2.1%). CONCLUSION: Despite a higher severity of illness at baseline, this phase IV open-label long-term study in Belgian ICUs shows consistent results with previous studies with DAA. Importantly, most of the surviving patients at day 90 were staying at home.

Acute eosinophilic pneumonia associated with intramuscular administration of progesterone as luteal phase support after IVF: case report.

We report two cases of acute eosinophilic pneumonia induced by i.m. administration of progesterone used as luteal phase support after IVF. For both patients, the symptoms began 3 weeks after the first injection of progesterone. Both patients were in respiratory distress, and one of them required ventilatory assistance for a week, with 5 days in the intensive care unit. Symptoms improved as the i.m. form was shifted to a vaginal form of progesterone together with the administration of corticosteroids. Sesame oil (used as excipient) and benzyl alcohol (used as preservative) could both be incriminated in the development of the hypersensitivity reaction. The need for luteal phase support is clearly established in IVF cycles with GnRH agonist protocols, and progesterone is the generally recommended compound. However, there is no definitive consensus regarding the optimal route of administration of progesterone. These two cases of acute drug-induced disease show that the use of i.m. progesterone can be associated with a severe morbidity in otherwise healthy young patients. This is an additional argument to advocate the use of vaginal progesterone as luteal support in IVF.

Effects of alpha - and beta -adrenergic stimulation on hepatosplanchnic perfusion and oxygen extraction in endotoxic shock.

OBJECTIVE: To examine the effects of adrenergic stimulation on hepatosplanchnic perfusion, oxygen extraction, and tumor necrosis factor-alpha production during endotoxic shock. DESIGN: In vivo, prospective, randomized, controlled, repeated-measures, experimental study. SETTING: Experimental physiology laboratory in a university teaching hospital. SUBJECTS: Twenty-one anesthetized and mechanically ventilated dogs. INTERVENTIONS: An intrapericardial catheter was positioned. Catheters for blood sampling were inserted into the right femoral artery, hepatic vein, portal vein, and pulmonary artery. Ultrasonic flow probes were placed around the portal vein, the hepatic artery, the mesenteric artery, the left renal artery, and the left femoral artery. Animals received 2 mg/kg of Escherichia coli endotoxin, followed by fluid resuscitation. Seven dogs received intravenous isoproterenol (0.1 microg/kg x min(-1)), seven received phenylephrine (1 microg/kg x min(-1)), and seven served as controls. Thirty minutes later, cardiac tamponade was introduced to study organ perfusion and tissue oxygen extraction capabilities. MAIN RESULTS: The isoproterenol group had a higher cardiac index and stroke index and lower systemic vascular resistance than the other groups. The phenylephrine group had a higher arterial pressure but a lower cardiac index than the isoproterenol group. The isoproterenol group had a higher hepatic artery blood flow than the other groups and a higher portal and mesenteric flow than the control group. Liver and gut mucosal blood flow was greater in the isoproterenol than in the phenylephrine group. The isoproterenol group had a lower global critical oxygen delivery than the other groups (8.8 +/- 1.3 vs. 13.1 +/- 2.0 (control) and 11.8 +/- 3.3 mL/kg x min(-1) (phenylephrine); both p < .05) and a higher liver critical oxygen extraction ratio than the control group. Isoproterenol tended to attenuate, but phenylephrine significantly increased, blood tumor necrosis factor levels. CONCLUSIONS: During endotoxic shock, beta-stimulation can improve hepatosplanchnic perfusion and enhance tissue oxygen extraction capabilities, whereas alpha-stimulation does not. In addition, alpha-adrenergic stimulation can increase tumor necrosis factor levels.

Hemodynamic responses to successful weaning from mechanical ventilation after cardiovascular surgery.

Weaning from mechanical ventilation is usually associated with an increase in oxygen consumption (VO2), which may stress the cardiovascular system. We studied relative changes in the cardiac index and oxygen extraction ratio (EO2) during successful weaning in patients after cardiac surgery (n = 52), cardiac transplantation (n = 17), or abdominal aortic surgery (n = 11). Cardiac index was determined by the thermodilution technique and arterial and mixed venous blood gases were obtained before and 30 min after the start of weaning through a T-piece. The cardiovascular changes were evaluated in 42 patients in whom VO2 (calculated by Fick's equation) increased by more than 10%. Cardiac index increased more after abdominal aortic surgery (from 3.27 +/- 0.77 to 4.44 +/- 0.581 min(-1) m(-2), p < 0.01) than after cardiac surgery (from 2.53 +/- 0.59 to 2.87 +/- 0.46 1 min(-1) m(-2), p < 0.01) or cardiac transplantation (from 2.99 +/- 0.64 to 3.33 +/- 0.741 min(-1) m(-2), p < 0.05). EO2 remained stable in patients after aortic surgery (from 25.9 +/- 7.1 to 25.2 +/- 5.6 %, NS) but increased slightly after cardiac surgery (from 33.3 +/- 6.1 to 37.3 +/- 6.4%, NS) and significantly after cardiac transplantation (from 25.8 +/- 4.1 to 28.2 +/- 4.0%, p < 0.05). Hence the cardiovascular response to weaning from mechanical ventilation may vary according to the type of surgery.

Lactate production by the lungs in acute lung injury.

Arteriovenous differences in lactate (AVLAC) across the lungs are usually small and close to zero. However, it has recently been reported that the lungs can produce increased amounts of lactate in some patients with acute respiratory distress syndrome (ARDS). The aim of this study was to evaluate lactate production in various types of acute lung injury requiring mechanical ventilation and hemodynamic monitoring. Since the differences involved are usually small, minor errors in lactate measurement could greatly influence AVLAC. Based on an analysis of these errors (see text for details), we averaged five arterial and venous samples for each measurement. We investigated 122 patients: 43 with acute lung injury (ALI), nine with cardiogenic pulmonary edema (CPE), 37 with bronchopneumonia (BPN), seven with single lung transplantation (LTX), and 26 with other causes of respiratory failure (OTHER). There was no difference in arterial lactate between the various groups. AVLAC was higher in patients with ALI than in the other groups (0.20+/-0.23 versus 0.07+/-0.11 mEq/L). In patients with ALI, AVLAC was proportional to the Murray's lung injury score (-0.032+/-0.032x; r = 0.46, p < 0.01). Lung lactate production was calculated as the product of the cardiac index times AVLAC and was significantly higher in patients with ALI than in the other groups (0.69+/-0.88 versus 0.19+/-0.30 mEq/min; p < 0.05). In patients with ALI, lung lactate production was inversely related to the PaO2/FIO2 (1.42 - 0.005x; r = 0.35, p < 0.05) but directly related to the venous admixture (-0.36 + 0.003x; r = 0.49, p < 0.01) and the lung injury score (-0.19 + 0.36x; r = 0.45, p < 0.01). Lung lactate production was not significantly related to arterial lactate levels. These data indicate that AVLAC and lung lactate production can be increased in patients with ARDS but remain within the normal range in other types of respiratory failure.

Monitoring gastric mucosal carbon dioxide pressure using gas tonometry: in vitro and in vivo validation studies.

BACKGROUND: Saline gastric tonometry of carbon dioxide has been proposed as a means to assess the adequacy of splanchnic perfusion. However, this technique has several disadvantages, including the long time interval needed for gases to reach equilibrium in saline milieu. Thus the authors evaluated a system that uses a gas-filled instead of a saline-filled gastric balloon. METHODS: In vitro, we simultaneously placed two tonometry catheters in an equilibration water bath maintained at a predetermined and constant pressure of carbon dioxide (P(CO2)). The first catheter's balloon was filled with air and the second with saline. The performance of gas tonometry was tested by comparing the P(CO2) measurements of the bath obtained via gas tonometry (PgCO2) to the P(CO2) measurements of direct bath samples (PbathCO2). These results were also compared with the P(CO2) measurements obtained simultaneously by saline tonometry (PsCO2). The response time of gas versus saline tonometry was also studied. In vivo, the performance of gas tonometry was tested comparing the measurements of gastric intramucosal P(CO2) obtained by gas tonometry (PgCO2) at different equilibration times with those obtained by saline tonometry (PsCO2) using an equilibration time of 30 min. Two nasogastric tonometry catheters were placed simultaneously in seven stable patients in the intensive care unit. The first balloon was filled with air and the second with saline. RESULTS: In vitro, there was a close correlation between PgCO2 and PbathCO2, for each level of PbathCO2, and for each different gas equilibration time. For an equilibration time of 10 min at a PbathCO2 level of approximately 40 mmHg, the bias of the gas device defined as the mean of the differences between PbathCO2 and PgCO2 and its precision defined as the standard deviation of the bias, were -0.3 mmHg and 0.7 mmHg, respectively. Using the same definitions, the bias and precision of saline tonometry were 11.2 mmHg and 1.4 mmHg, respectively. If the equilibration time-dependent correction factor provided by the catheter manufacturer for saline tonometry was applied, the bias and precision were -6.9 mmHg and 2.9 mmHg, respectively. In vivo, using an equilibration time of 10 min for gas and 30 min for saline tonometry, there was a close correlation between the two techniques (r2 = 0.986). A Bland and Altman analysis revealed a bias (+/- 2 SD) of 0.1 +/- 6.8 mmHg. The correlation between the two methods was not improved if we prolonged the equilibration time of the gas tonometer. CONCLUSIONS: Gas tonometry is comparable to saline tonometry for measuring gastric intramucosal P(CO2). Because gas tonometry is easier to automate, it may offer advantages over saline tonometry.

Atrial septostomy under transesophageal guidance in a patient with primary pulmonary hypertension and absent right superior vena cava.

A patient presenting primary pulmonary hypertension and absent right superior vena cava underwent blade/balloon atrial septostomy as palliative therapy. Due to the anomaly of the venous drainage system, only transesophageal echocardiography allowed the performance of the maneuvre.

Relation between oxygen consumption and oxygen delivery in patients after cardiac surgery.

The relative contributions of oxygen delivery (DO2) and oxygen extraction (O2ER) to the increase in cellular oxygen uptake (VO2) after cardiopulmonary bypass were studied prospectively in 36 patients after coronary artery bypass grafting (n = 18), valve replacement (n = 17), and removal of a left atrial tumor (n = 1). VO2 was calculated from the Fick equation and DO2 from thermodilution cardiac output and arterial oxygen content. During the first 24 h after cardiac surgery, there was a strong relation between VO2 and DO2 (VO2 = 28 + 0.27 x DO2, r = 0.79, P < 0.0001) but not between VO2 and oxygen extraction. Mixed venous oxygen saturation (SVO2) was usually reduced when cardiac index was below 2.0 L.min-1.m-2. Patients with a prolonged intensive care unit course (> 24 h) had lower cardiac index and lower SVO2 than the other patients. Therefore, the progressive increase in VO2 after cardiac surgery is accomplished primarily by an increase in cardiac output and DO2. It is usually when cardiac function is compromised that O2ER increases and SVO2 decreases.

High or low dose steroid therapy for acute renal transplant rejection after prophylactic OKT3 treatment: a prospective randomized study.

In this prospective randomized study, acute renal transplant rejections occurring in patients who received prophylactic OKT3 therapy were treated with either 3 pulses of 8 mg/kg methylprednisolone (MPS) in an alternate-day regimen (total dose 25 mg/kg in 1 week, H group, n = 24) or 5 daily pulses of 3 mg/kg MPS (total dose 17 mg/kg, L group, n = 22). Acute rejection was proven by biopsy in more than 85% of cases in both groups. No difference was observed in rejection reversal (H 88%, L 91%), graft losses in the following 3 months (H 11%, L 4%) or the time evolution of the serum creatinine levels. The number (H 14, L 21) as well as the nature and severity of infections were similar in both groups. Only one death occurred in a patient who received OKT3 rescue therapy for corticoresistant rejections and developed Epstein-Barr virus (EBV)-related lymphoma. In conclusion, low dose MPS pulses appear as effective and safe as a higher dose to reverse acute rejection occurring after OKT3 prophylaxis. Thus, we favour the use of the low dose regimen in these patients.