Plethysmographic dynamic indices predict fluid responsiveness in septic ventilated patients

Objectives: In septic patients, reliable non-invasive predictors of fluid responsiveness are needed. We hypothesised that the respiratory changes in the amplitude of the plethysmographic pulse wave (ΔPPLET) would allow the prediction of changes in cardiac index following volume administration in mechanically ventilated septic patients. Design: Prospective clinical investigation. Setting: An 11-bed hospital medical intensive care unit. Patients: Twenty-three deeply sedated septic patients mechanically ventilated with tidal volume ≥ 8 ml/kg and equipped with an arterial catheter and apulse oximetry plethysmographic sensor. Interventions: Respiratory changes in pulse pressure (ΔPP), ΔPPLET and cardiac index (transthoracic Doppler echocardiography) were determined before and after volume infusion of colloids (8 ml/kg). Measurements and main results: Twenty-eight volume challenges were performed in 23 patients. Before volume expansion, ΔPP correlated with ΔPPLET (r 2 = 0.71, p < 0.001). Changes in cardiac index after volume expansion significantly (p < 0.001) correlated with baseline ΔPP (r 2 = 0.76) and ΔPPLET (r 2 = 0.50). The patients were defined as responders to fluid challenge when cardiac index increased by at least 15% after the fluid challenge. Such an event occurred 18 times. Before volume challenge, aΔPP value of 12% and aΔPPLET value of 14% allowed discrimination between responders and non-responders with sensitivity of 100% and 94% respectively and specificity of 70% and 80% respectively. Comparison of areas under the receiver operator characteristic curves showed that ΔPP and ΔPPLET predicted similarly fluid responsiveness. Conclusion: The present study found ΔPPLET to be as accurate as ΔPP for predicting fluid responsiveness in mechanically ventilated septic patient

Effects of hemorrhage on gastrointestinal oxygenation

Objectives: (1) To demonstrate that metabolic parameters are better indicators of tissue hypoxia than regional and whole oxygen consumption (VO2). (2) To compare intramucosal pH (pHi) in different gastrointestinal segments. Design: Prospective, interventional study. Setting: Research laboratory at a university center. Subjects: Fourteen anesthetized, mechanically ventilated dogs. Interventions: Twenty milliliters per kilogram bleeding. Measurements and main results: We placed pulmonary, aortic and mesenteric venous catheters, and an electromagnetic flow probe in the superior mesenteric artery, and gastric, jejunal and ileal tonometers to measure flows, arterial and venous blood gases and lactate, and intramucosal PCO2. We calculated systemic and intestinal oxygen transport (DO2) and consumption (VO2), pHi and arterial minus intramucosal PCO2 (ΔPCO2). Then, we bled the dogs and repeated the measurements after 30 min. Systemic and intestinal DO2 fell (26.0±7.3 versus 8.9±2.6 and 71.9±17.3 versus 24.6±9.6 ml/min per kg, respectively, p<0.0001). Systemic and intestinal VO2 remained unchanged (5.5±1.3 versus 5.4±1.3 and 15.7±5.0 versus 14.9±5.3 ml/min per kg, respectively). Gastric, jejunal and ileal pHi (7.13±0.11 versus 6.96±0.17, 7.18±0.06 versus 6.97±0.15, 7.12±0.11 versus 6.94±0.14, p<0.05) and ΔPCO2 (21±13 versus 35±23, 15±5 versus 33±16, 23±17 versus 38±20, p<0.05) changed accordingly. Arterial and mesenteric venous lactate and their difference, rose significantly (1.7±0.9 versus 3.7±1.4 and 1.8±0.8 versus 4.3±1.5 mmol/l, 0.1±0.6 versus 0.6±0.7 mmol/l, p<0.05). Conclusions: During hemorrhage, systemic and intestinal VO2 remained stable. However, hyperlactatemia and intramucosal acidosis evidenced anaerobic metabolism. pHi changes paralleled in the three intestinal segments.Facultad de Ciencias Médica

Increased blood flow prevents intramucosal acidosis in sheep endotoxemia: a controlled study

Introduction Increased intramucosal–arterial carbon dioxide tension (PCO₂) difference (∆PCO₂) is common in experimental endotoxemia. However, its meaning remains controversial because it has been ascribed to hypoperfusion of intestinal villi or to cytopathic hypoxia. Our hypothesis was that increased blood flow could prevent the increase in ∆PCO₂. Methods In 19 anesthetized and mechanically ventilated sheep, we measured cardiac output, superior mesenteric blood flow, lactate, gases, hemoglobin and oxygen saturations in arterial, mixed venous and mesenteric venous blood, and ileal intramucosal PCO₂ by saline tonometry. Intestinal oxygen transport and consumption were calculated. After basal measurements, sheep were assigned to the following groups, for 120 min: (1) sham (n = 6), (2) normal blood flow (n = 7) and (3) increased blood flow (n = 6). Escherichia coli lipopolysaccharide (5 µg/kg) was injected in the last two groups. Saline solution was used to maintain blood flood at basal levels in the sham and normal blood flow groups, or to increase it to about 50% of basal in the increased blood flow group. Results In the normal blood flow group, systemic and intestinal oxygen transport and consumption were preserved, but ∆PCO₂ increased (basal versus 120 min endotoxemia, 7 ± 4 versus 19 ± 4 mmHg; P < 0.001) and metabolic acidosis with a high anion gap ensued (arterial pH 7.39 versus 7.35; anion gap 15 ± 3 versus 18 ± 2 mmol/l; P < 0.001 for both). Increased blood flow prevented the elevation in ∆PCO2 (5 ± 7 versus 9 ± 6 mmHg; P = not significant). However, anion-gap metabolic acidosis was deeper (7.42 versus 7.25; 16 ± 3 versus 22 ± 3 mmol/l; P < 0.001 for both). Conclusions In this model of endotoxemia, intramucosal acidosis was corrected by increased blood flow and so might follow tissue hypoperfusion. In contrast, anion-gap metabolic acidosis was left uncorrected and even worsened with aggressive volume expansion. These results point to different mechanisms generating both alterations.Facultad de Ciencias Médica

End-tidal CO<SUB>2</SUB> pressure determinants during hemorrhagic shock

Objectives: To examine the relationship between end-tidal CO2 (PETCO2) and its physiological determinants, pulmonary blood flow (cardiac output, CO) and CO2 production (VCO2), in a model of hemorrhagic shock during fixed minute ventilation. Design and setting: Prospective, observational study in a research laboratory at a university center. Subjects and interventions: Six anesthetized, intubated, and mechanically ventilated mongrel dogs. Progressive stepwise bleeding. Measurements and results: We continuously measured PETCO2 with a capnograph, pulmonary artery blood flow with an electromagnetic flow probe, arterial oxygen saturation (SaO2) with a fiberoptic catheter, and oxygen consumption (VO2) and VCO2 by expired gases analysis. Oxygen delivery (DO2) was continuously calculated from pulmonary blood flow and SaO2. We studied the correlation of PETCO2 with CO and VCO2 in each individual experiment. We also calculated the critical point in the relationships PETCO2/DO2 and VO2/DO2 by the polynomial method. As expected, PETCO2 was correlated with CO. The best fit was logarithmic in all experiments (median r 2=0.90), showing that PETCO2 decrease is greater in lowest flow states. PETCO2 was correlated with VCO2, but the best fit was linear (median r 2=0.77). Critical DO2 for PETCO2 and VO2 was 8.0±3.3 and 6.3±2.5 ml.min–1.kg–1, respectively (NS). Conclusions: Our data reconfirm the relationship between PETCO2 and CO during hemorrhagic shock. The relatively greater decrease in PETCO2 at lowest CO levels could represent diminished CO2 production during the period of VO2 supply dependency.Facultad de Ciencias Médica

Effects of hemorrhage on gastrointestinal oxygenation

Objectives: (1) To demonstrate that metabolic parameters are better indicators of tissue hypoxia than regional and whole oxygen consumption (VO2). (2) To compare intramucosal pH (pHi) in different gastrointestinal segments. Design: Prospective, interventional study. Setting: Research laboratory at a university center. Subjects: Fourteen anesthetized, mechanically ventilated dogs. Interventions: Twenty milliliters per kilogram bleeding. Measurements and main results: We placed pulmonary, aortic and mesenteric venous catheters, and an electromagnetic flow probe in the superior mesenteric artery, and gastric, jejunal and ileal tonometers to measure flows, arterial and venous blood gases and lactate, and intramucosal PCO2. We calculated systemic and intestinal oxygen transport (DO2) and consumption (VO2), pHi and arterial minus intramucosal PCO2 (ΔPCO2). Then, we bled the dogs and repeated the measurements after 30 min. Systemic and intestinal DO2 fell (26.0±7.3 versus 8.9±2.6 and 71.9±17.3 versus 24.6±9.6 ml/min per kg, respectively, p<0.0001). Systemic and intestinal VO2 remained unchanged (5.5±1.3 versus 5.4±1.3 and 15.7±5.0 versus 14.9±5.3 ml/min per kg, respectively). Gastric, jejunal and ileal pHi (7.13±0.11 versus 6.96±0.17, 7.18±0.06 versus 6.97±0.15, 7.12±0.11 versus 6.94±0.14, p<0.05) and ΔPCO2 (21±13 versus 35±23, 15±5 versus 33±16, 23±17 versus 38±20, p<0.05) changed accordingly. Arterial and mesenteric venous lactate and their difference, rose significantly (1.7±0.9 versus 3.7±1.4 and 1.8±0.8 versus 4.3±1.5 mmol/l, 0.1±0.6 versus 0.6±0.7 mmol/l, p<0.05). Conclusions: During hemorrhage, systemic and intestinal VO2 remained stable. However, hyperlactatemia and intramucosal acidosis evidenced anaerobic metabolism. pHi changes paralleled in the three intestinal segments.Facultad de Ciencias Médica

Increased blood flow prevents intramucosal acidosis in sheep endotoxemia: a controlled study

Introduction Increased intramucosal–arterial carbon dioxide tension (PCO₂) difference (∆PCO₂) is common in experimental endotoxemia. However, its meaning remains controversial because it has been ascribed to hypoperfusion of intestinal villi or to cytopathic hypoxia. Our hypothesis was that increased blood flow could prevent the increase in ∆PCO₂. Methods In 19 anesthetized and mechanically ventilated sheep, we measured cardiac output, superior mesenteric blood flow, lactate, gases, hemoglobin and oxygen saturations in arterial, mixed venous and mesenteric venous blood, and ileal intramucosal PCO₂ by saline tonometry. Intestinal oxygen transport and consumption were calculated. After basal measurements, sheep were assigned to the following groups, for 120 min: (1) sham (n = 6), (2) normal blood flow (n = 7) and (3) increased blood flow (n = 6). Escherichia coli lipopolysaccharide (5 µg/kg) was injected in the last two groups. Saline solution was used to maintain blood flood at basal levels in the sham and normal blood flow groups, or to increase it to about 50% of basal in the increased blood flow group. Results In the normal blood flow group, systemic and intestinal oxygen transport and consumption were preserved, but ∆PCO₂ increased (basal versus 120 min endotoxemia, 7 ± 4 versus 19 ± 4 mmHg; P < 0.001) and metabolic acidosis with a high anion gap ensued (arterial pH 7.39 versus 7.35; anion gap 15 ± 3 versus 18 ± 2 mmol/l; P < 0.001 for both). Increased blood flow prevented the elevation in ∆PCO2 (5 ± 7 versus 9 ± 6 mmHg; P = not significant). However, anion-gap metabolic acidosis was deeper (7.42 versus 7.25; 16 ± 3 versus 22 ± 3 mmol/l; P < 0.001 for both). Conclusions In this model of endotoxemia, intramucosal acidosis was corrected by increased blood flow and so might follow tissue hypoperfusion. In contrast, anion-gap metabolic acidosis was left uncorrected and even worsened with aggressive volume expansion. These results point to different mechanisms generating both alterations.Facultad de Ciencias Médica

Effect of Hydrocortisone on Mortality and Organ Support in Patients With Severe COVID-19: The REMAP-CAP COVID-19 Corticosteroid Domain Randomized Clinical Trial.

Importance: Evidence regarding corticosteroid use for severe coronavirus disease 2019 (COVID-19) is limited. Objective: To determine whether hydrocortisone improves outcome for patients with severe COVID-19. Design, Setting, and Participants: An ongoing adaptive platform trial testing multiple interventions within multiple therapeutic domains, for example, antiviral agents, corticosteroids, or immunoglobulin. Between March 9 and June 17, 2020, 614 adult patients with suspected or confirmed COVID-19 were enrolled and randomized within at least 1 domain following admission to an intensive care unit (ICU) for respiratory or cardiovascular organ support at 121 sites in 8 countries. Of these, 403 were randomized to open-label interventions within the corticosteroid domain. The domain was halted after results from another trial were released. Follow-up ended August 12, 2020. Interventions: The corticosteroid domain randomized participants to a fixed 7-day course of intravenous hydrocortisone (50 mg or 100 mg every 6 hours) (n = 143), a shock-dependent course (50 mg every 6 hours when shock was clinically evident) (n = 152), or no hydrocortisone (n = 108). Main Outcomes and Measures: The primary end point was organ support-free days (days alive and free of ICU-based respiratory or cardiovascular support) within 21 days, where patients who died were assigned -1 day. The primary analysis was a bayesian cumulative logistic model that included all patients enrolled with severe COVID-19, adjusting for age, sex, site, region, time, assignment to interventions within other domains, and domain and intervention eligibility. Superiority was defined as the posterior probability of an odds ratio greater than 1 (threshold for trial conclusion of superiority >99%). Results: After excluding 19 participants who withdrew consent, there were 384 patients (mean age, 60 years; 29% female) randomized to the fixed-dose (n = 137), shock-dependent (n = 146), and no (n = 101) hydrocortisone groups; 379 (99%) completed the study and were included in the analysis. The mean age for the 3 groups ranged between 59.5 and 60.4 years; most patients were male (range, 70.6%-71.5%); mean body mass index ranged between 29.7 and 30.9; and patients receiving mechanical ventilation ranged between 50.0% and 63.5%. For the fixed-dose, shock-dependent, and no hydrocortisone groups, respectively, the median organ support-free days were 0 (IQR, -1 to 15), 0 (IQR, -1 to 13), and 0 (-1 to 11) days (composed of 30%, 26%, and 33% mortality rates and 11.5, 9.5, and 6 median organ support-free days among survivors). The median adjusted odds ratio and bayesian probability of superiority were 1.43 (95% credible interval, 0.91-2.27) and 93% for fixed-dose hydrocortisone, respectively, and were 1.22 (95% credible interval, 0.76-1.94) and 80% for shock-dependent hydrocortisone compared with no hydrocortisone. Serious adverse events were reported in 4 (3%), 5 (3%), and 1 (1%) patients in the fixed-dose, shock-dependent, and no hydrocortisone groups, respectively. Conclusions and Relevance: Among patients with severe COVID-19, treatment with a 7-day fixed-dose course of hydrocortisone or shock-dependent dosing of hydrocortisone, compared with no hydrocortisone, resulted in 93% and 80% probabilities of superiority with regard to the odds of improvement in organ support-free days within 21 days. However, the trial was stopped early and no treatment strategy met prespecified criteria for statistical superiority, precluding definitive conclusions. Trial Registration: ClinicalTrials.gov Identifier: NCT02735707

Hyperoxemia and excess oxygen use in early acute respiratory distress syndrome: insights from the LUNG SAFE study

Contains fulltext : 218568.pdf (publisher's version ) (Open Access)BACKGROUND: Concerns exist regarding the prevalence and impact of unnecessary oxygen use in patients with acute respiratory distress syndrome (ARDS). We examined this issue in patients with ARDS enrolled in the Large observational study to UNderstand the Global impact of Severe Acute respiratory FailurE (LUNG SAFE) study. METHODS: In this secondary analysis of the LUNG SAFE study, we wished to determine the prevalence and the outcomes associated with hyperoxemia on day 1, sustained hyperoxemia, and excessive oxygen use in patients with early ARDS. Patients who fulfilled criteria of ARDS on day 1 and day 2 of acute hypoxemic respiratory failure were categorized based on the presence of hyperoxemia (PaO2 > 100 mmHg) on day 1, sustained (i.e., present on day 1 and day 2) hyperoxemia, or excessive oxygen use (FIO2 >/= 0.60 during hyperoxemia). RESULTS: Of 2005 patients that met the inclusion criteria, 131 (6.5%) were hypoxemic (PaO2 < 55 mmHg), 607 (30%) had hyperoxemia on day 1, and 250 (12%) had sustained hyperoxemia. Excess FIO2 use occurred in 400 (66%) out of 607 patients with hyperoxemia. Excess FIO2 use decreased from day 1 to day 2 of ARDS, with most hyperoxemic patients on day 2 receiving relatively low FIO2. Multivariate analyses found no independent relationship between day 1 hyperoxemia, sustained hyperoxemia, or excess FIO2 use and adverse clinical outcomes. Mortality was 42% in patients with excess FIO2 use, compared to 39% in a propensity-matched sample of normoxemic (PaO2 55-100 mmHg) patients (P = 0.47). CONCLUSIONS: Hyperoxemia and excess oxygen use are both prevalent in early ARDS but are most often non-sustained. No relationship was found between hyperoxemia or excessive oxygen use and patient outcome in this cohort. TRIAL REGISTRATION: LUNG-SAFE is registered with ClinicalTrials.gov, NCT02010073