Systems approach to heart-lung interactions.
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Cardiac Output↗
Biomedical subjects
M R Pinsky
Publications and source records attributed to M R Pinsky.
Modeling of asynchronous myocardial contraction by effective stroke volume analysis.
UNLABELLED: Left ventricular (LV) regional wall motion abnormalities (RWMA) are not easily quantified. We describe a model for quantifying RWMA by referencing regional amplitude and phase angle changes to global LV systole in eight anesthetized, open-chest dogs. Regional and total LV volumes (conductance catheter), regional shortening (epicardial piezoelectric crystals), and LV pressure were measured before, during, and after transient esmolol-induced apical RWMA. Regional phase angle (alpha) was defined as the relative distance, measured in degrees, that regional minimal volume differs from global end-systole. We compared maximal stroke volume (SV) with effective SV (that portion of regional SV contributing to total LV SV). Regional effective SV was also calculated from our model as the product of cosine alpha and regional maximal SV. Esmolol delayed apical end-systolic alpha (14.3 degrees +/- 11.4 degrees versus 35.7 degrees +/- 8.0 degrees baseline versus esmolol, P < 0.05) and decreased apical effective SV (2.4 +/- 0.3 versus 1.7 +/- 0.3 mL, P < 0.05), while apical maximal SV and total LV SV were not altered. Piezoelectric crystal dimension changes mirrored regional SV changes. We conclude that effective SV and phase angle analysis are more sensitive measures of regional myocardial dysfunction when RWMA exist than are measures of maximal regional SV. IMPLICATIONS: In a dog model of regional myocardial dyskinesis induced by esmolol, effective regional stroke volume and phase angle analyses are more sensitive measures of regional myocardial dysfunction than measures of maximal regional stroke volume that do not account for phase shifts.
Animals↗
Esmolol-induced regional wall motion abnormalities do not affect regional ventricular elastances.
UNLABELLED: The effect of regional wall motion abnormalities (RWMA) on regional and global left ventricular (LV) elastances has not been defined. To induce RWMA, we infused esmolol (9 mg) into the left anterior descending coronary artery in eight anesthetized open-chest canine preparations. Global and regional stroke volumes and end-systolic pressure-volume relationships (LV conductance catheter) and pressure-length relationships (sonomicrometer crystals) were measured in dysfunctional (apical) and normal (basilar) LV regions at baseline, during esmolol infusion, and after treatment with a systemic dobutamine infusion (4 microg. kg(-1). min(-1)) and combined dobutamine-esmolol. Esmolol induced apical dyskinesis, as evidenced by reduced effective apical stroke volumes and stroke work, a parallel right-shift of the apical regional, global end-systolic pressure-volume relationships, and increased regional and global LV volumes (P < 0.05). However, global and regional elastances remained unchanged. Dobutamine increased global and apical regional elastances, but did not increase regional volumes. During the infusion of combined esmolol-dobutamine, apical elastance and volumes increased compared with baseline (P < 0.05), but apical regional stroke work decreased. Thus, esmolol-induced RWMA were associated with cardiac dilation but not with decreased regional or global elastances. IMPLICATIONS: Regional and global elastances and maximal stroke volumes may not identify esmolol-induced left ventricular regional dysfunction in dogs. The primary effect of asynchrony of regional contraction is global cardiac dilation. Systemic dobutamine infusion increases regional and global left ventricular elastances but does not reverse regional wall motion abnormality-induced cardiac dilation.
Animals↗
Hemodynamic effects of synchronized high-frequency jet ventilation compared with low-frequency intermittent positive-pressure ventilation after myocardial revascularization.
BACKGROUND: The purpose of this prospective study was to examine the effect on cardiac performance of selective increases in airway pressure at specific points of the cardiac cycle using synchronized high-frequency jet ventilation (sync-HFJV) delivered concomitantly with each single heart beat compared with controlled mechanical ventilation in 20 hemodynamically stable, deeply sedated patients immediately after coronary artery bypass graft. METHODS: Five 30-min sequential ventilation periods were used interspersing controlled mechanical ventilation with sync-HFJV twice to control for time and sequencing effects. Sync-HFJV was applied using a driving pressure, which generated a tidal volume resulting in gas exchanges close to those obtained on controlled mechanical ventilation and associated with the maximal mixed venous oxygen saturation. Hemodynamic variables including cardiac output, mixed venous oxygen saturation and vascular pressures were recorded at the end of each ventilation period. RESULTS: The authors found that in 20 patients, hemodynamic changes induced by controlled mechanical ventilation and by sync-HFJV were similar. Cardiac index did not change (mean +/- SD for controlled mechanical ventilation: 2.6 +/- 0.7 l x min(-1) x m(-2); for sync-HFJV: 2.7 +/- 0.7 l x min(-1) x m(-2); P value not significant). This observation persisted after stratification according to baseline left-ventricular contractility, as estimated by ejection fraction. CONCLUSIONS: The authors conclude that after coronary artery bypass graft, if gas-exchange values are maintained within normal range, sync-HFJV does not result in more favorable hemodynamic support than controlled mechanical ventilation. These findings contrast with the beneficial effects of sync-HFJV, resulting in marked hypocapnia, on cardiac performance observed in patients with terminal left-ventricular failure.
Adult↗
Short-term and long-term outcome prediction with the Acute Physiology and Chronic Health Evaluation II system after orthotopic liver transplantation.
OBJECTIVE: To evaluate the relationship between the postoperative Acute Physiology and Chronic Health Evaluation (APACHE) II score and mortality at hospital discharge and at 1 yr in liver transplant recipients. POPULATION: Adult orthotopic liver transplant (OLTX) recipients (n = 599) admitted to the intensive care unit postoperatively at a university hospital. METHODS: The cohort was split randomly into development and validation sets. Three models were compared for each end point: a) the original APACHE II slope with the original APACHE II postgastrointestinal surgery intercept; b) the original APACHE II slope with an OLTX-specific intercept generated from the development set; and c) an OLTX-specific slope and intercept generated from the development set. Goodness-of-fit and calibration were assessed by the Hosmer-Lemeshow C statistic (where p>.05 suggests good fit) and standardized mortality ratios. Discrimination was assessed by receiver operator characteristic area under the curve analysis. MEASUREMENTS AND MAIN RESULTS: Hospital and 1-yr mortality rates were 9.9% and 15.9%, respectively. The APACHE II score was strongly associated with mortality (chi-square, p<.0001), but when used with the original equation, it significantly overestimated hospital mortality (standardized mortality ratio, 0.73 [confidence interval, 0.58-0.99]). Using the OLTX-specific approaches, goodness-of-fit for both hospital and 1-yr mortality was good (p = .2-.57) but discrimination was only moderate (receiver operator characteristic area under the curve, 0.675-0.723). CONCLUSIONS: APACHE II is a good predictor of short- and long-term mortality after liver transplantation, especially when using OLTX-specific coefficients. Because fit and calibration were better than discrimination, APACHE II will be most useful in the prediction of risk for groups of patients (e.g., in clinical trials or institutional comparisons) rather than for individuals. This study raises the possibility that APACHE II may be useful for long-term mortality prediction in other critically ill populations. The overestimation of mortality using the original equation suggests that orthotopic liver transplantation, by reversing the underlying pathophysiology, may modify risk.
APACHE↗
Accuracy of mucosal pH and mucosal-arterial carbon dioxide tension for detecting mesenteric hypoperfusion in acute canine endotoxemia.
OBJECTIVE: To determine the level of mucosal-arterial Pco2 (Pco2 gap) that is both sensitive and specific for the detection of mesenteric hypoperfusion as defined by either a >50% reduction in portal blood flow or release of lactate by the gut. DESIGN: Animal experiment. SUBJECTS: Seven anesthetized, intubated, mechanically ventilated, and surgically instrumented mongrel dogs. INTERVENTION: Escherichia coli endotoxin (1 mg/kg) given intravenously for 5 mins. MEASUREMENTS AND MAIN RESULTS: Tonometric Pco2, arterial blood gases, arterial and portal venous lactates, and portal and systemic hemodynamic variables were measured. Mucosal pH (pHi) was calculated according to the manufacturers' instructions. From these data, receiver operating characteristics were calculated. Although animals were resuscitated to maintain a constant cardiac output, portal flow decreased from 350+/-101 to 152+/-75 mL/min (p<.01) and the gut released lactate into the portal circulation in all animals. Pco2 gap increased from 13.1+/-3.9 to 40.2+/-39.2 torr (p<.01) and was inversely correlated with portal blood flow (r2 = .20; p<.05). For detection of a >50% reduction in portal blood flow, a Pco2 gap of 20 torr yielded a maximum accuracy of 67% (sensitivity, 55%; specificity, 73%) and was less accurate than a pHi of 7.20, which yielded a maximum accuracy of 76% (sensitivity, 90%; specificity, 70%), although this difference was not significant (p = .24). There was also a correlation between pHi and portal blood flow (r2 = .31; p<.01). For detection of lactate release by the gut, a Pco2 gap of 20 torr was also 67% accurate (sensitivity, 53%; specificity, 78%), whereas a pHi of 7.10 achieved an accuracy of 64% (sensitivity, 40%; specificity, 83%), which was not significantly different. CONCLUSION: Pco2 gap measurements are neither sensitive nor specific for mesenteric hypoperfusion with regard to total gut blood flow reductions of >50% or the release of lactate into the portal circulation.
Animals↗
Medical students can learn the basic application, analytic, evaluative, and psychomotor skills of critical care medicine.
OBJECTIVE: To determine whether fourth-year medical students can learn the basic analytic, evaluative, and psychomotor skills needed to initially manage a critically ill patient. DESIGN: Student learning was evaluated using a performance examination, the objective structured clinical examination (OSCE). Students were randomly assigned to one of two clinical scenarios before the elective. After the elective, students completed the other scenario, using a crossover design. SETTING: Five surgical intensive care units in a tertiary care university teaching hospital. PARTICIPANTS: Forty fourth-year medical students enrolled in the critical care medicine (CCM) elective. INTERVENTIONS: All students evaluated a live "simulated critically ill" patient, requested physiologic data from a nurse, ordered laboratory tests, received data in real time, and intervened as they deemed appropriate. MEASUREMENTS AND MAIN RESULTS: Student performance of specific behavioral objectives was evaluated at five stations. They were expected to a) assess airway, breathing, and circulation in appropriate sequence; b) prepare a manikin for intubation, obtain an acceptable airway on the manikin, demonstrate bag-mouth ventilation, and perform acceptable laryngoscopy and intubation; c) provide appropriate mechanical ventilator settings; d) manage hypotension; and e) request and interpret pulmonary artery data and initiate appropriate therapy. OSCEs were videotaped and reviewed by two faculty members masked to time of examination. A checklist of key behaviors was used to evaluate performance. The primary outcome measure was the difference in examination score before and after the rotation. Secondary outcomes included the difference in scores at each rotation. The mean preelective score was 57.0%+/-8.3% compared with 85.9%+/-7.4% (p<.0001) after the elective. Significant improvement was demonstrated at each station except station I. CONCLUSION: Fourth-year medical students without a CCM elective do not possess the basic cognitive and psychomotor skills necessary to initially manage critically ill patients. After an appropriate 1-month CCM elective, students' thinking and application skills required to initially manage critically ill patients improved markedly, as demonstrated by an OSCE using a live simulated "patient" and manikin.
Catheterization, Swan-Ganz↗
Right atrial pressure predicts hemodynamic response to apneic positive airway pressure.
OBJECTIVE: To evaluate if the preexistant filling state, assessed by right atrial pressure (RAP), pulmonary artery occlusion pressure (PAOP), and right ventricular end-diastolic volume index (EDVI), would define the subsequent hemodynamic effects of increases in airway pressure (Paw). DESIGN: Prospective open clinical study. SETTING: Postoperative intensive care unit, university hospital. PATIENTS: Twenty-two consecutive ventilator-dependent patients with mild to severe acute lung injury with Murray scores (scoring infiltrates on chest radiograph, oxygenation index, lung compliance, and the level of positive end-expiratory pressure) ranging from 0.5 to 3.0 without history of preexisting cardiopulmonary disease. INTERVENTIONS: Paw varied during apnea from 0 to 10, 20, and 30 cm H2O using inspiratory hold maneuvers of 15 secs. MEASUREMENTS AND MAIN RESULTS: Cardiac index and right ventricular ejection fraction were measured by the thermodilution technique. We made measurements in triplicate using manual injection of iced saline. Right ventricular volumes were calculated. Increasing Paw induced variable changes in cardiac index among subjects (+6% to -43% change from baseline 0 cm H2O Paw values), which correlated with percentage changes in both stroke index (r2 = .89) and right ventricular EDVI (r2 = .75), whereas heart rate and right ventricular ejection fraction did not change. The change in cardiac index from 0 to 30 cm H2O Paw correlated with baseline values for RAP, PAOP, and right ventricular EDVI (r2 = .68, .43, and .34, respectively, p < 0.01). Increases in RAP correlated with lung compliance if baseline RAP was >10 mm Hg but did not if it was < or =10 mm Hg. Similarly, patients with baseline RAP < or =10 mm Hg had a greater decrease in cardiac index than patients with a RAP >10 mm Hg (for 30 cm H2O Paw: -30% +/- 9% vs. -8% +/- 7%, p < .01). CONCLUSIONS: Apneic positive Paw decreased cardiac output mainly by reducing venous return. From the investigated filling variables, RAP was most sensitive in predicting the hemodynamic response, followed by PAOP and right ventricular EDVI. Patients with RAP < or =10 mm Hg, if subjected to aggressive positive pressure ventilation, are at risk of hemodynamic deterioration and organ hypoperfusion.
Adult↗
Effects of positive end-expiratory pressure on hemodynamics and indocyanine green kinetics in patients after orthotopic liver transplantation.
OBJECTIVE: To determine the impact of positive end-expiratory pressure (PEEP) ventilation on hemodynamics and a clinical test for assessment of dynamic liver performance in patients undergoing orthotopic liver transplantation (OLT). DESIGN: Prospective, descriptive patient study. SETTING: University hospital intensive care unit. PATIENTS: A total of 25 patients after OLT. INTERVENTIONS: All patients were intubated and mechanically ventilated with biphasic positive airway pressure. The effects of three different randomly chosen levels of PEEP (0 cm H2O, 5 cm H2O, and 10 cm H2O) were studied in the immediate postoperative period. MEASUREMENTS AND MAIN RESULTS: Systemic hemodynamics, arterial and venous blood gas analyses, and plasma disappearance rate of indocyanine green (ICG(PDR)), using the transpulmonary indicator dilution technique, were obtained simultaneously. For data evaluation, patients were grouped retrospectively according to their hemodynamic response to PEEP (Group A and Group B). In Group A (n = 13), PEEP did not alter cardiac index. In Group B (n = 11), PEEP levels of 5 cm H2O and 10 cm H2O significantly reduced cardiac index and oxygen delivery. ICG(PDR) remained statistically unchanged in both groups. CONCLUSIONS: Short-term pressure-controlled ventilation with PEEP levels of up to 10 cm H2O does not exert detrimental effects on systemic hemodynamics in OLT patients and does not interfere with ICG(PDR). However, it remains to be determined whether these findings could be confirmed under the application of higher PEEP levels over a longer period of time and whether they could be of clinical relevance for the use of indocyanine green as a dynamic liver function test.
Coloring Agents↗
Auto-positive end-expiratory pressure during tracheal gas insufflation: testing a hypothetical model.
OBJECTIVE: The major benefit of tracheal gas insufflation (TGI) is an increase in CO2 elimination efficiency by removal of CO2 from the anatomical deadspace. In conjunction with mechanical ventilation, TGI may also alter variables that affect CO2 elimination, such as minute ventilation and peak airway pressure (peak Paw) and cause the development of auto-positive end-expiratory pressure (auto-PEEP). We tested the hypothesis that TGI-induced auto-PEEP alters ventilatory variables. We predicted that TGI-induced auto-PEEP offsets the beneficial effects of TGI on CO2 elimination and that keeping total PEEP (ventilator PEEP + auto-PEEP) constant enhances the CO2 elimination efficiency afforded by TGI. DESIGN: Prospective study of two series of patients with acute respiratory distress syndrome receiving mechanical ventilation. SETTING: Intensive care units at a university medical center. PATIENTS: Each series consisted of eight sequential hypercapnic patients. INTERVENTIONS: In series 1, we examined the effect of continuous TGI at 0 and 10 L/min on PaCO2, without compensating for the development of auto-PEEP. In series 2, we examined this same effect of continuous TGI while reducing ventilator PEEP to keep total PEEP constant. TGI-induced auto-PEEP was calculated based on dynamic compliance measurements during zero TGI flow conditions (deltaV/deltaP) after averaging the two baseline values for peak Paw and tidal volume and assuming compliance did not change between the zero TGI and TGI flow conditions (deltaVTGI/deltaPTGI). MEASUREMENTS AND MAIN RESULTS: In series 1, total PEEP increased from 13.2 +/- 3.2 cm H2O to 17.8 +/- 3.5 cm H2O without compensation for auto-PEEP (p = .01). PaCO2 decreased (p = .03) from 56.2 +/- 10.6 mm Hg (zero TGI) to 52.9 +/- 9.3 mm Hg (TGI at 10 L/min), a 6% decrement. In series 2, total PEEP was unchanged (p = NS). PaCO2 decreased (p = .03) from 59.5 +/- 10.4 mm Hg (zero TGI) to 52.2 +/- 8.3 mm Hg (TGI at 10 L/min), a 12% decrement. There was no significant change in PaO2; there were no untoward hemodynamic effects in either series. CONCLUSIONS: These data are consistent with the hypothesis that mechanical ventilation + TGI causes an increase in auto-PEEP that can blunt CO2 elimination. In addition to the ventilator modifications necessary to keep ventilatory variables constant when TGI is used, it is also necessary to reduce ventilator PEEP to keep total PEEP constant and further enhance CO2 elimination efficiency.
Aged↗
Estimating cardiac filling pressure in mechanically ventilated patients with hyperinflation.
OBJECTIVE: When positive end-expiratory pressure (PEEP) is applied, the intracavitary left ventricular end-diastolic pressure (LVEDP) exceeds the LV filling pressure because pericardial pressure exceeds 0 at end-expiration. Under those conditions, the LV filling pressure is itself better reflected by the transmural LVEDP (tLVEDP) (LVEDP minus pericardial pressure). By extension, end-expiratory pulmonary artery occlusion pressure (eePAOP), as an estimate of end-expiratory LVEDP, overestimates LV filling pressure when pericardial pressure is >0, because it occurs when PEEP is present. We hypothesized that LV filling pressure could be measured from eePAOP by also knowing the proportional transmission of alveolar pressure to pulmonary vessels calculated as index of transmission = (end-inspiratory PAOP--eePAOP)/(plateau pressure--total PEEP). We calculated transmural pulmonary artery occlusion pressure (tPAOP) with this equation: tPAOP = eePAOP--(index of transmission x total PEEP). We compared tPAOP with airway disconnection nadir PAOP measured during rapid airway disconnection in subjects undergoing PEEP with and without evidence of dynamic pulmonary hyperinflation. DESIGN: Prospective study. SETTING: Medical intensive care unit of a university hospital. PATIENTS: We studied 107 patients mechanically ventilated with PEEP for acute respiratory failure. Patients without dynamic pulmonary hyperinflation (group A; n = 58) were analyzed separately from patients with dynamic pulmonary hyperinflation (group B; n = 49). INTERVENTION: Transient airway disconnection. MEASUREMENTS AND MAIN RESULTS: In group A, tPAOP (8.5+/-6.0 mm Hg) and nadir PAOP (8.6+/-6.0 mm Hg) did not differ from each other but were lower than eePAOP (12.4+/-5.6 mm Hg; p < .05). The agreement between tPAOP and nadir PAOP was good (bias, 0.15 mm Hg; limits of agreement, -1.5-1.8 mm Hg). In group B, tPAOP (9.7+/-5.4 mm Hg) was lower than both nadir PAOP and eePAOP (12.1+/-5.4 and 13.9+/-5.2 mm Hg, respectively; p < .05 for both comparisons). The agreement between tPAOP and nadir PAOP was poor (bias, 2.3 mm Hg; limits of agreement, -0.2-4.8 mm Hg). CONCLUSIONS: Indexing the transmission of proportional alveolar pressure to PAOP in the estimation of LV filling pressure is equivalent to the nadir method in patients without dynamic pulmonary hyperinflation and may be more reliable than the nadir PAOP method in patients with dynamic pulmonary hyperinflation.
Aged↗
Effect of ibuprofen and diethylcarbamazine on the hemodynamic and inflammatory response to endotoxin in the dog.
We studied the effects of pretreatment with either ibuprofen (15 mg/kg), diethylcarbamazine (DEC, 15 mg/kg), or vehicle, on the hemodynamic, hematologic, and serum tumor necrosis factor-alpha (TNF-alpha) and interleukin (IL)-6 responses to a bolus Escherichia coli endotoxin infusion (2 mg/kg) in 21 pentobarbital-anesthetized dogs (n = 7 each group). Hematologic and cytokine data were collected before and 0.5, 1, and 3 h after endotoxin infusion. Endotoxin decreased arterial pressure (P(a)), cardiac output (CO), total leukocyte (WBC) and platelet counts, and increased lactate, TNF-alpha, and IL-6. TNF-alpha levels peaked at 1 h and decreased by 3 h, whereas IL-6 remained elevated. Ibuprofen abolished the endotoxin-induced changes in P(a) and lactate, but did not alter the initial decrease in CO, WBC, and platelets or the increase in TNF-alpha and IL-6. DEC did not alter the response to endotoxin, although the DEC group had higher TNF-alpha and IL-6 levels before endotoxin infusion compared to controls. We conclude that the cardiovascular effects of ibuprofen in the canine model of acute endotoxemia are not due to suppression of the systemic inflammatory response.
Animals↗
Cardiac contractility is not depressed in early canine endotoxic shock.
We investigated effects of acute endotoxemia (Escherichia coli endotoxin, 1 mg/kg, intravenously) on left ventricular (LV) function in the first 4 h after induction of endotoxic shock in anesthetized canine preparations (n = 7 each, endotoxin and control groups). LV pressure and conductance (volume) catheters were used to construct pressure-volume loops. Transient inferior vena cava occlusion was used to rapidly and reversibly alter LV end-diastolic volume. LV contractility was assessed from the slope of the LV end-systolic pressure-volume relationship (Ees) and from preload-recruitable stroke work (PRSW), and from their change (DeltaEes and DeltaPRSW, respectively, measured at 2 and 4 h only), in response to a dobutamine infusion (5 microg/kg/min). Diastolic function and arterial tone were assessed as the maximal negative change in filling pressure versus time (max -dP/dt), filling rate, and arterial elastance (Ea), respectively. Ees, PRSW, Ea, diastolic function, and hemodynamics were measured hourly. Endotoxemia induced an immediate hypotensive, hyperdynamic, tachycardic state with progressive lactic acidosis. By 2.5 h after endotoxin infusion, heart rate returned to preendotoxin and control levels, but the other changes remained. However, no change occurred in LV Ees, DeltaEes, PRSW, DeltaPRSW, diastolic function, or Ea during the 4-h measurement interval. The cardiovascular collapse seen during the first 4 h of endotoxemia is therefore not due even partly to alterations in LV contractility.
Animals↗
The effect of intensive plasma water exchange by hemofiltration on hemodynamics and soluble mediators in canine endotoxemia.
High volume hemofiltration (HVHF) (200 ml/kg/h) improves hemodynamics in experimental septic shock but is difficult to apply clinically. Accordingly, we studied whether less intensive HVHF (80 ml/kg/h) can still improve hemodynamics in experimental septic shock. We also investigated its effect on the serum concentrations of several inflammatory mediators, including endothelin (ET-1), endotoxin (LPS), tumor necrosis factor-alpha (TNF-alpha), and 6-keto prostaglandin F(1alpha) (6-kepto PGF(1alpha)). Sixteen anesthetized dogs were connected to a continuous veno-venous hemofiltration (CVVH) (filtration: 80 ml/kg/h) or sham circuit and endotoxin (0.5 mg/kg) was infused intravenously over 5 min. Hemodynamic variables were measured at baseline and at 15, 45, 90, and 180 min. The major hemodynamic finding was that endotoxin-induced hypotension was significantly attenuated by intensive CVVH (p < 0.04). Changes in cardiac output and right ventricular ejection fraction were equal in both groups. ET-1 levels, but not LPS, TNF-alpha, or 6-keto PGF(1alpha), were lower during CVVH (p = 0.042). Endotoxin or TNF-alpha were not found in the ultrafiltrate. Median clearances of ET-1 and 6-keto PGF(1alpha) during intensive CVVH were 8.8 and 25.9 ml/m, respectively. We conclude that intensive CVVH attenuates the early component of endotoxin-induced hypotension and reduces serum concentrations of endothelin-1. The effect of CVVH on blood pressure is not explained by convective clearance of the mediators in question.
6-Ketoprostaglandin F1 alpha↗
Relation between respiratory changes in arterial pulse pressure and fluid responsiveness in septic patients with acute circulatory failure.
In mechanically ventilated patients with acute circulatory failure related to sepsis, we investigated whether the respiratory changes in arterial pressure could be related to the effects of volume expansion (VE) on cardiac index (CI). Forty patients instrumented with indwelling systemic and pulmonary artery catheters were studied before and after VE. Maximal and minimal values of pulse pressure (Pp(max) and Pp(min)) and systolic pressure (Ps(max) and Ps(min)) were determined over one respiratory cycle. The respiratory changes in pulse pressure (DeltaPp) were calculated as the difference between Pp(max) and Pp(min) divided by the mean of the two values and were expressed as a percentage. The respiratory changes in systolic pressure (DeltaPs) were calculated using a similar formula. The VE-induced increase in CI was >/= 15% in 16 patients (responders) and < 15% in 24 patients (nonresponders). Before VE, DeltaPp (24 +/- 9 versus 7 +/- 3%, p < 0.001) and DeltaPs (15 +/- 5 versus 6 +/- 3%, p < 0.001) were higher in responders than in nonresponders. Receiver operating characteristic (ROC) curves analysis showed that DeltaPp was a more accurate indicator of fluid responsiveness than DeltaPs. Before VE, a DeltaPp value of 13% allowed discrimination between responders and nonresponders with a sensitivity of 94% and a specificity of 96%. VE-induced changes in CI closely correlated with DeltaPp before volume expansion (r(2) = 0. 85, p < 0.001). VE decreased DeltaPp from 14 +/- 10 to 7 +/- 5% (p < 0.001) and VE-induced changes in DeltaPp correlated with VE-induced changes in CI (r(2) = 0.72, p < 0.001). It was concluded that in mechanically ventilated patients with acute circulatory failure related to sepsis, analysis of DeltaPp is a simple method for predicting and assessing the hemodynamic effects of VE, and that DeltaPp is a more reliable indicator of fluid responsiveness than DeltaPs.
Adolescent↗
Tracheal gas insufflation. Limits of efficacy in adults with acute respiratory distress syndrome.
In mechanically ventilated adults with acute respiratory distress syndrome (ARDS), peak airway pressures (Paw(peak)) above 35 cm H(2)O may increase the risk of barotrauma or volutrauma. Tracheal gas insufflation (TGI), an adjunctive ventilatory technique, may facilitate a reduction in set inspiratory pressure in these patients, and thereby in the tidal volume (VT) and Paw(peak) used in their ventilation, without a consequent increase in arterial carbon dioxide tension (PaCO(2)). The purpose of this study was to: (1) assess the limits of efficacy of continuous TGI at two levels of decreased mechanical ventilatory support; and (2) determine an appropriate time interval after initiation of TGI at which to evaluate response. We prospectively studied eight adults with ARDS and increased airway pressures (40.2 +/- 2.7 cm H(2)O) who were managed with pressure-control ventilation (PCV). After obtaining baseline ventilatory and hemodynamic measures, we initiated TGI at 10 L/min, adjusting ventilator positive-end expiratory pressure (PEEP) to maintain baseline VT, and decreased the set inspiratory pressure by 5 cm H(2)O. Data were obtained after 30 and 60 min. Set inspiratory pressure was then decreased by an additional 5 cm H(2)O (total: 10 cm H(2)O), and data were again obtained after 30 min. Baseline (zero TGI) measures were then again recorded. Thirty minutes after decreasing the set inspiratory pressure by 5 cm H(2)O with TGI at 10 L/min, there was a 15% decrease in Paw(peak) and a 16% decrease in VT as compared with their baseline values. However, Pa(CO(2)) remained constant (59 +/- 10 mm Hg versus 57 +/- 6 mm Hg) (p = NS). There was no change in Pa(O(2)) or in hemodynamic variables, and no differences between variables, at 30 min versus 60 min in seven subjects. The remaining subject did not tolerate the reduction in set inspiratory pressure for 60 min. Thirty minutes after the set inspiratory pressure was decreased by 10 cm H(2)O with TGI at 10 L/min, there was a 26% decrease in Paw(peak) and a 26% decrease in VT. However, Pa(CO(2)) increased by 19% and Pa(O(2)) decreased by 13%. Six subjects completed this phase of the protocol for 30 min, and one subject completed it for 60 min. TGI can be used to rapidly facilitate a 5 cm H(2)O reduction in set inspiratory pressure without an increase in Pa(CO(2)). The ability to achieve a 5 cm H(2)O reduction in set inspiratory pressure without adverse physiologic effects was evident within 30 min. Attempts to further reduce set inspiratory pressure were not successful.
Acute Disease↗
NF-kappaB expression in mononuclear cells of patients with sepsis resembles that observed in lipopolysaccharide tolerance.
The expression of NF-kappaB was studied in freshly isolated peripheral blood mononuclear cells (PBMC) of patients with severe sepsis and major trauma. The expression of p65p50 heterodimer, the active form of NF-kappaB, was significantly reduced for all patients as compared with control subjects. The p50p50 homodimer, an inhibitory form of NF-kappaB, was reduced in the survivors of sepsis and in patients with trauma. Subsequent in vitro stimulation of PBMC with lipopolysaccharide (LPS) did not induce further NF-kappaB nuclear translocation: the survivors of sepsis and trauma patients showed low expression of both p65p50 and p50p50, whereas nonsurvivors of sepsis showed a predominance of the inactive homodimer and a low p65p50/p50p50 ratio when compared with control subjects. In the later group of patients there was a reverse correlation between plasma IL-10 levels and the p65p50/p50p50 ratio after in vitro LPS stimulation (r = -0.8, p = 0.04). The reduced expression of nuclear NF-kappaB was not due to its inhibition by IkappaBalpha, as very low expression of IkappaBalpha, as well as low levels of p65 and p50 were found in the cytoplasm of PBMC from patients with sepsis and trauma when compared with control subjects. These results demonstrate that upon LPS activation, PBMC of patients with systemic inflammatory response syndrome show patterns of NF-kappaB expression that resemble those reported during LPS tolerance: global down-regulation of NF-kappaB in survivors of sepsis and trauma patients and the presence of large amounts of the inactive homodimer in the nonsurvivors of sepsis.
Adolescent↗
Immune balance in critically ill patients.
The systemic inflammatory response reflects the non-specific clinical expression of a profound activation of the body's immune responsive elements. Immune activation and immune suppression coexist in the blood of patients with severe sepsis. It is their interaction and the resultant host parenchymal responses that ultimately define the course of sepsis. Importantly, neither profound immune activation (pro-inflammatory) or immune suppression (anti-inflammatory) characterize the dominant process. Rather, there is a combined low grade pro-inflammatory state associated with an immune hyporesponsiveness that defines the usual immunologic state of the patient with severe sepsis.
Critical Illness↗