Evolution of lactate/pyruvate and arterial ketone body ratios in the early course of catecholamine-treated septic shock.

OBJECTIVES: To measure arterial lactate/pyruvate (L/P) and arterial ketone body ratios as reflection of cytoplasmic and mitochondrial redox state at different stages of catecholamine-treated septic shock and compare them with normal and pathologic values obtained in patients in shock who have decreased oxygen transport (cardiogenic shock), and to assess the relationship between the time course of lactate, L/P ratio, and mortality in septic shock. DESIGN: Prospective, observational human study. SETTING: A university intensive care unit. PATIENTS: Sixty consecutive adult patients who developed septic shock and lactic acidosis requiring the administration of vasopressors. Twenty patients in the intensive care unit without shock, sepsis, and hypoxia and with normal lactate values and 10 patients with cardiogenic shock were also studied. MEASUREMENTS: Hemodynamic measurements, arterial and mixed venous blood gases, arterial lactate and pyruvate concentrations, and arterial ketone body ratio were measured within 4 hrs after the introduction of catecholamine and 24 hrs later. MAIN RESULTS: Fifteen patients (25%) died within the first 24 hrs of septic shock, and these early fatalities had a higher blood lactate (12.2+/-3 versus 4.6+/-1.3 mmol/L; p<.01) concentration and a higher L/P ratio (37+/-4 versus 20+/-1; p<.01) than those who died later. No difference was found for arterial ketone body ratio (0.41+/-0.1 versus 0.50+/-0.06). Forty-five patients survived >24 hrs including 25 survivors and 20 nonsurvivors. Although there was no difference between survivors and nonsurvivors in initial lactate concentration (4.1+/-0.4 and 4.6+/-0.3, respectively), L/P ratio (19+/-1 and 20+/-1, respectively), and arterial ketone body ratio (0.5+/-0.06 and 0.52+/-0.07, respectively), blood lactate and L/P ratio significantly decreased during the first 24 hrs in the survivors (2.8+/-0.4 and 14+/-1, respectively; p<.05). and were stable in the nonsurvivors (4+/-0.3 and 22+/-1, respectively) Although returning to normal values after 24 hrs in survivors and nonsurvivors, arterial ketone body ratio was higher in survivors (1.72+/-0.17 versus 1.09+/-0.15; p<.05). Lactate and L/P ratio were closely correlated (r2 = .8, p<.0001). In the cardiogenic shock group, lactate concentration was 4+/-1 mmol/L, L/P ratio was 40+/-6, and arterial ketone body ratio was 0.2+/-0.05. The mortality rate was 60%. CONCLUSIONS: The main result of the present study is that hemodynamically unstable patients with sepsis needing catecholamine therapy had a lactic acidosis with an elevated L/P ratio and a decreased arterial ketone body ratio, suggesting a decrease in cytoplasmic and mitochondrial redox state. The duration of lactic acidosis is associated with the development of multiple organ failure and death.

Comparison of systemic and regional effects of dobutamine and dopexamine in norepinephrine-treated septic shock.

OBJECTIVES: To compare the effects of dobutamine and dopexamine on systemic hemodynamics, lactate metabolism, renal function and the intramucosal-arterial PCO(2) gap in norepinephrine-treated septic shock. DESIGN: A prospective, interventional, randomized clinical trial. SETTING: Adult medical/surgical intensive care unit in a university hospital. PATIENTS: After volume resuscitation, 24 patients were treated with norepinephrine alone titrated to obtain a mean arterial pressure of 75 mmHg and a cardiac index greater than 3. 5 l/min(-1). m(-2). INTERVENTIONS: Patients were randomized to receive an infusion of dobutamine (n = 12) (5 microg/kg per min) or dopexamine (n = 12) (1 microg/kg per min). MEASUREMENTS AND MAIN RESULTS: Baseline measurements included: hemodynamic parameters, renal parameters (diuresis, creatinine clearance and urinary sodium excretion), gastric mucosal-arterial PCO(2) gap, arterial and mixed venous gases and arterial lactate and pyruvate levels. These measurements were repeated after 1 (H(1)), 4 (H(4)) and 24 (H(24)) h. No difference was found between dobutamine and dopexamine among H(0) and H(1), H(4) and H(24) values for hemodynamics. Dobutamine and dopexamine at low doses had no significant effect on mean arterial pressure, heart rate, cardiac index, oxygen delivery, oxygen consumption and pulmonary artery occlusion pressure. No patients developed arrhythmia or electrocardiographic signs of myocardial ischemia. After 4 and 24 h lactate concentration decreased in the dobutamine group from 2.4 +/- 1 mmol/l to 1.7 +/- 0. 7 mmol/l and 1.5 +/- 0.4 mmol/l, respectively, while it increased in the dopexamine group from 2.3 +/- 1 mmol/l to 2.7 +/- 1 mmol/l after 4 h and returned to baseline values after 24 h (2.2 +/- 0.6). After 24 h the lactate/pyruvate ratio decreased in the dobutamine group from 15 +/- 5 to 12 +/- 3 (p < 0.05) while it was unchanged in the dopexamine group (from 16 +/- 6 to 17 +/- 4). Arterial pH increased in the dobutamine group from 7.35 +/- 0.05 to 7.38 +/- 0.07 (p < 0. 05) while it was unchanged in the dopexamine group (from 7.34 +/- 0. 01 to 7.35 +/- 0.10). The PCO(2) gap decreased after 1 and 4 h in both the dobutamine and dopexamine groups (p < 0.05 with respect to baseline). When looking at individual responses, however, patients from both groups exhibited an increased gastric PCO(2) gap. No difference was found between dobutamine and dopexamine for renal parameters. CONCLUSIONS: In norepinephrine-treated septic shock, low doses of neither dobutamine nor dopexamine caused significant effects on systemic hemodynamics and renal function and both dobutamine and dopexamine inconsistently improved the PCO(2) gap. The present results support the need for individual measurement of the effects of catecholamine on the PCO(2) gap.

[Collective oxygen therapy and disaster medicine]. / Oxygénothérapie collective et médecine de catastrophe.

The distribution of oxygen to many victims can be necessary all along the medical help chain: operations of extraction, stand up, recovery, transport, life supporting care, surviving and transportation in mobile processing formations installed to proximity of the site, evacuations by road or by fly. Moreover, hospital in situation of crisis has an increased oxygen consumption (especially for ventilators). An estimable need calculation, a census of stocking and distribution ways have to allow to adapt resources to needs. Proposed solutions are the strengthening of vehicles in oxygen tanks, utilization of liquid oxygen tanks in large mobile formations and particular procedures to supply hospital crisis situation.

Reversal of late septic shock with supraphysiologic doses of hydrocortisone.

OBJECTIVES: Preliminary studies have suggested that low doses of corticosteroids might rapidly improve hemodynamics in late septic shock treated with catecholamines. We examined the effect of hydrocortisone on shock reversal, hemodynamics, and survival in this particular setting. DESIGN: Prospective, randomized, double-blind, placebo-controlled study. SETTING: Two intensive care units of a University hospital. PATIENTS: Forty-one patients with septic shock requiring catecholamine for >48 hrs. INTERVENTIONS: Patients were randomly assigned either hydrocortisone (100 mg i.v. three times daily for 5 days) or matching placebo. MEASUREMENTS AND MAIN RESULTS: Reversal of shock was defined by a stable systolic arterial pressure (>90 mm Hg) for > or =24 hrs without catecholamine or fluid infusion. Of the 22 hydrocortisone-treated patients and 19 placebo-treated patients, 15 (68%) and 4 (21%) achieved 7-day shock reversal, respectively, a difference of 47% (95% confidence interval 17% to 77%; p = .007). Serial invasive hemodynamic measurements for 5 days did not show significant differences between both groups. At 28-day follow-up, reversal of shock was higher in the hydrocortisone group (p = .005). Crude 28-day mortality was 7 (32%) of 22 treated patients and 12 (63%) of 19 placebo patients, a difference of 31% (95% confidence interval 1% to 61%; p = .091). Shock reversal within 7 days after the onset of corticosteroid therapy was a very strong predictor of survival. There were no significant differences in outcome in responders and nonresponders to a short corticotropin test. The respective rates of gastrointestinal bleeding and secondary infections did not differ between both groups. CONCLUSIONS: Administration of modest doses of hydrocortisone in the setting of pressor-dependent septic shock for a mean of >96 hrs resulted in a significant improvement in hemodynamics and a beneficial effect on survival. These beneficial effects do not appear related to adrenocortical insufficiency.

[Complications of vascular surgery]. / Complications de la chirurgie vasculaire.

Vascular surgery, which in certain life-threatening situations is the only possible therapeutic option, has progressed considerably since its beginning in the 1950s. Because of the constant progression of vascular diseases, this surgery will present, in the forthcoming years, a major public health problem. Because of advances in medico-surgical management, evermore elderly and frail patients can be treated. Perioperative mortality is constantly decreasing, but much progress remains to be accomplished to prevent, avoid or treat, postoperative complications. They are common and serious in these typical patients with cardiovascular diseases (men over 50 years of age, heavy smokers, atheromatous ...). The AA divide these complications into 3 main groups depending on the surgical procedure: abdominal aortic surgery, carotid surgery and arterial and venous surgery of the lower limbs. There is much data on abdominal aortic surgery because these long and complex procedures produce repercussions often involving many systems. The postoperative complications are treated according to the system they involve: cardiovascular, the most serious, respiratory, the commonest, alimentary, neurological, renal, others, as well as combined systems. The AA do not deal with the specific problems associated with cardiac and cardio-thoracic surgery. The AA discuss the different epidemiological findings of the large surgical series published in the 1970s and 1980s. The more recent literature analyses the relationship between preoperative risk factors (atheroma, COAD, hypertension ...), peroperative problems (surgical difficulties, emergencies, massive transfusions, others) and the corresponding postoperative morbidity. Thus a few general outlines of the physiopathology of these different complications emerge. In the light of these notions the few proposed methods will be evaluated in order to improve the preoperative condition of the vascular patient. The AA also review the relevance of the preoperative investigation in patients for vascular surgery. All these measures aim at reducing the incidence and severity of perioperative morbidity.

Gastric versus duodenal feeding and gastric tonometric measurements.

OBJECTIVE: To compare the influence of gastric and postpyloric enteral feeding on the gastric tonometric PCO2 gap (tonometric PCO2 - PaCO2). DESIGN: A prospective, clinical trial. SETTING: Two intensive care units in a university hospital. PATIENTS: Twenty patients undergoing mechanical ventilation and enteral feeding without catecholamines, sepsis, or sign of hypoxia. INTERVENTIONS: Patients were randomized to receive feeding through the tonometer (gastric group), or through a postpyloric tube (postpyloric group). MEASUREMENTS AND MAIN RESULTS: The patients received tube feeding at a rate of 50 mL/hr during 4 hrs. Baseline measurements included: mean arterial pressure, heart rate, tonometric parameters, arterial gases, and arterial lactate concentration. Except for lactate concentration, these measurements were repeated after 1 and 4 hrs of enteral feeding and 2 hrs after stopping enteral feeding. During the study, arterial pH and PaCO2 did not change. During enteral feeding, the PCO2 gap increased in the gastric group from a mean of 7+/-5 to 17+/-14 (SD) torr (0.9 0.7 to 2.3+/-1.9 kPa) (p< .O01) and did not change in the postpyloric group (5+/-5 to 3+/-1 torr [0.7+/-0.7 to 0.4+/-0.1 kPa]). Two hours after stopping enteral feeding, the PCO2 gap was still increased in the gastric group (15+/-9 vs. 7+/-5 torr [2.0+/-1.2 vs. 0.9+/-0.7 kPa]) (p < .01). CONCLUSION: The results indicate that gastric enteral feeding increased the PCO2 gap. However, postpyloric enteral feeding does not interact with gastric tonometric measurements and should be used when using gastric tonometry in enterally fed patients.

Dobutamine improves the adequacy of gastric mucosal perfusion in epinephrine-treated septic shock.

OBJECTIVE: To assess the effects of dobutamine at a rate of 5 micrograms/kg/min on hemodynamics and gastric intramucosal acidosis in patients with hyperdynamic septic shock treated with epinephrine. DESIGN: A prospective, interventional, clinical trial. SETTING: An adult, 16-bed medical/surgical intensive care unit of a university hospital. PATIENTS: Twenty septic shock patients with a mean arterial pressure of > 75 mm Hg and a cardiac index of > 3.5 L/min/m2. INTERVENTIONS: After baseline measurements (H0), each patient received dobutamine at a rate of 5 micrograms/kg/min. Baseline measurements included: hemodynamic parameters, tonometric parameters, arterial and mixed venous gases, and arterial lactate concentrations. These measurements were repeated after 1 (H1), 2 (H2), and 3 (H3) hrs. After H2 measurements, dobutamine was stopped. The patients were separated into two groups according to their PCO2 gap (tonometer PCO2-PaCO2). The increased PCO2 gap group was defined by a PCO2 gap > 8 torr (> 1.1 kPa) (n = 13), and the normal PCO2 gap group by a PCO2 gap < or = 8 torr (< or = 1.1 kPa)(n = 7). MEASUREMENTS AND MAIN RESULTS: Dobutamine at 5 micrograms/kg/min had no significant effects on mean arterial pressure, heart rate, cardiac index, systemic vascular resistance, oxygen delivery, and oxygen consumption in epinephrine-treated septic shock. No patients developed arrhythmia or electrocardiographic signs of myocardial ischemia. During dobutamine infusion, arterial lactate concentration decreased from 5.1 +/- 0.4 in the increased PCO2 gap group and 4.2 +/- 0.4 in the normal PCO2 gap group to 3.9 +/- 0.3 and 3.5 +/- 0.3 mmol/L, respectively (p < .01). The PCO2 gap decreased and gastric intramucosal pH increased in the increased PCO2 gap group from 12 +/- 0.8 (1.6 +/- 0.1 kPa) to 3.5 +/- 0.8 torr (0.5 +/- 0.1 kPa) (p < .01) and from 7.11 +/- 0.03 to 7.18 +/- 0.02 (p < .01), respectively, and did not change in the normal PCO2 gap group. After stopping dobutamine infusion, the PCO2 gap and intramucosal pH returned to baseline values in the increased PCO2 gap group. CONCLUSION: The addition of 5 micrograms/kg/min of dobutamine added to epinephrine in hyperdynamic septic shock selectively improved the adequacy of gastric mucosal perfusion without modification in systemic hemodynamics.

Comparison of norepinephrine and dobutamine to epinephrine for hemodynamics, lactate metabolism, and gastric tonometric variables in septic shock: a prospective, randomized study.

OBJECTIVES: To compare the effects of norepinephrine and dobutamine to epinephrine on hemodynamics, lactate metabolism, and gastric tonometric variables in hyperdynamic dopamine-resistant septic shock. DESIGN: A prospective, intervention, randomized clinical trial. SETTING: Adult medical/surgical intensive care unit in a university hospital. PATIENTS: 30 patients with a cardiac index (CI) > 3.51 x min(-1) x m(-2) and a mean arterial pressure (MAP) < or = 60 mmHg after volume loading and dopamine 20 microg/kg per min and either oliguria or hyperlactatemia. INTERVENTIONS: Patients were randomized to receive an infusion of either norepinephrine-dobutamine or epinephrine titrated to obtain an MAP greater than 80 mmHg with a stable or increased CI. MEASUREMENTS AND MAIN RESULTS: Baseline measurements included: hemodynamic and tonometric parameters, arterial and mixed venous gases, and lactate and pyruvate blood levels. These measurements were repeated after 1, 6, 12, and 24 h. All the patients fulfilled the therapeutic goals. No statistical difference was found between epinephrine and norepinephrine-dobutamine for systemic hemodynamic measurements. Considering metabolic and tonometric measurements and compared to baseline values, after 6 h, epinephrine infusion was associated with an increase in lactate levels (from 3.1 +/- 1.5 to 5.9 +/- 1.0 mmol/l;p < 0.01), while lactate levels decreased in the norepinephrine-dobutamine group (from 3.1 +/- 1.5 to 2.7 +/- 1.0 mmol/l). The lactate/pyruvate ratio increased in the epinephrine group (from 15.5 +/- 5.4 to 21 +/- 5.8; p < 0.01) and did not change in the norepinephrine-dobutamine group (13.8 +/- 5 to 14 +/- 5.0). Gastric mucosal pH (pHi) decreased (from 7.29 +/- 0.11 to 7.16 +/- 0.07; p < 0.01) and the partial pressure of carbon dioxide (PCO2) gap (tonometer PCO2-arterial PCO2) increased (from 10 +/- 2.7 to 14 +/- 2.7 mmHg; p < 0.01) in the epinephrine group. In the norepinephrine-dobutamine group pHi (from 7.30 +/- 0.11 to 7.35 +/- 0.07) and the PCO2 gap (from 10 +/- 3.0 to 4 +/- 2.0 mmHg) were normalized within 6 h (p < 0.01). The decrease in pHi and the increase in the lactate/pyruvate ratio in the epinephrine group was transient, since it returned to normal within 24 h. CONCLUSIONS: Considering the global hemodynamic effects, epinephrine is as effective as norepinephrine-dobutamine. Nevertheless, gastric mucosal acidosis and global metabolic changes observed in epinephrine-treated patients are consistent with a markedly inadequate, although transient, splanchnic oxygen utilization. The metabolic and splanchnic effects of the combination of norepinephrine and dobutamine in hyperdynamic dopamine-resistant septic shock appeared to be more predictable and more appropriate to the current goals of septic shock therapy than those of epinephrine alone.

Intracranial hypertension and adult respiratory distress syndrome: usefulness of tracheal gas insufflation.

The management of increased intracranial pressure (ICP) in patients with an associated acute lung injury is difficult. High levels of PaCO2 as tolerated for permissive hypercapnia are deleterious for cerebral circulation. In such circumstances, tracheal gas insufflation (TGI), which was recently proposed to reduce PaCO2, may be of benefit. We report the cases of two patients with severe adult respiratory distress syndrome and head trauma complicated with elevated ICP. The introduction of TGI decreased PaCO2 by 17 and 26%, decreased ICP, and increased calculated cerebral perfusion pressure. We conclude that TGI could be added to a pressure-targeted strategy of ventilatory management when severe adult respiratory distress syndrome was associated to an intracranial hypertension.

Hemodynamic and metabolic effects of rapid correction of hypophosphatemia in patients with septic shock.

STUDY OBJECTIVE: To examine the hemodynamic and metabolic short-term effects of hypophosphatemia correction in patients with septic shock receiving catecholamine therapy. DESIGN: Prospective, single cohort study. SETTING: ICU, university hospital. PATIENTS: Ten patients with septic shock and hypophosphatemia below 2 mg/dL. INTERVENTIONS: Infusion of glucose-1-phosphate solution (20 mmol of elemental phosphorus) for 60 min. MEASUREMENTS AND RESULTS: Hemodynamic, oxygen-derived, acid-base, and electrolyte parameters before and immediately after phosphate infusion. Left ventricular stroke work index increased significantly (22%) from a mean low value of 24 +/- 10 g/m2 without changes in filling pressures. Systolic arterial pressure improved by 12%. Arterial pH improved slightly but significantly. Ionized calcium level slightly decreased within the normal range values. Other parameters remained unchanged. CONCLUSIONS: Severe hypophosphatemia may be considered as a superimposed cause of myocardial depression, inadequate peripheral vasodilatation, and acidosis in septic shock. A rapid correction of hypophosphatemia is well tolerated and may have both myocardial and vascular beneficial effects. The magnitude of the response, however, is variable and unpredictable on the basis of serum phosphorus levels.

Therapeutic optimization including inhaled nitric oxide in adult respiratory distress syndrome in a polyvalent intensive care unit.

OBJECTIVE: To investigate the effects of inhaled nitric oxide (NO) in adult respiratory distress syndrome (ARDS) associated with a therapeutic optimization strategy on oxygen parameters, barotrauma, and evolution in a medical and surgical intensive care unit. DESIGN: Prospective study. MATERIALS AND METHODS: Twenty consecutive patients with ARDS were studied (Murray score 3.6 +/- 0.2). Eleven were surgical patients and nine were medical patients. All fulfilled the extracorporeal membrane oxygenation entry criteria. The APACHE II score predicted mortality was 39%. All were ventilated with FiO2 1 with positive end-expiratory pressure (PEEP) of 11 +/- 1 cm H2O. Therapeutic optimization included permissive hypercapnia, tracheal gas insufflation, prone position, continuous hemofiltration, treatment of infection, and pleural drainage. We used NO continuously inhaled at a concentration ranging from 5 to 10 ppm. MEASUREMENTS AND MAIN RESULTS: After 1 hour, inhaled NO improved PaO2 in all patients except one (78 +/- 11 to 130 +/- 25 mm Hg) (p < 0.05), allowing a reduction of FiO2 and PEEP. After 24 hours, mean pulmonary arterial pressure decreased from 31 +/- 3 to 25 +/- 2 mm Hg (p < 0.05). Systemic hemodynamics were unaffected. Oxygen delivery increased from 531 +/- 135 to 603 +/- 125 mL/minute/m-2 (p < 0.05). Barotraumatic lesions were present in only one patient. Reversal of ARDS was obtained in 16 patients, of whom 14 (70%) were discharged. CONCLUSIONS: This study was shorter to demonstrate an improvement in the survival rate. Nevertheless, these preliminary results are encouraging. Because of its safety, effectiveness, and easy use, inhaled NO should be used as a part of a therapeutic optimization protocol before considering more invasive and expensive procedures, such as extracorporeal respiratory support or intravascular oxygenation.