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M R Pinsky

Publications and source records attributed to M R Pinsky.

At least 19 recordsLinked to original sources
PubMed1999

Suppression of cytokine-mediated beta2-integrin activation on circulating neutrophils in critically ill patients.

The beta2 integrin CD11b plays a central role in inflammation and the systemic inflammatory response syndrome (SIRS). The CD11b molecule activates in two ways: the density of membrane-bound CD11b up-regulates and the molecule undergoes a conformational change that confers adhesiveness to counter-receptors. We studied the kinetics of CD11b activation in patients with SIRS. We found a significantly diminished CD11b activation in response to tumor necrosis factor alpha (TNF-alpha). This affected all circulating polymorphonuclear neutrophils (PMN) and was an intrinsic property of the cells and not due to antagonism by soluble TNF-alpha receptors or loss of cellular receptors for TNF-alpha. Diminished responsiveness correlated with the severity of organ failure and lasted for months in some patients but had no impact on mortality. We speculate that reduced CD11b responsiveness in SIRS contributes to the high risk of recurrent infection, but that it may also be protective against excessive PMN activation within the vascular space.

Adult↗
PubMed1999

Is there occult tissue ischemia in chronic end-stage liver disease?

Whether pathological oxygen supply dependency exists in patients with chronic end-stage liver disease (CESLD) is unknown, although the frequently occurring multiorgan dysfunction seen in these patients may be the result of occult tissue ischemia. In this study, 15 adult patients with CESLD were evaluated for the presence of pathological oxygen supply dependency and, thus, occult tissue ischemia before undergoing orthotopic liver transplantation. Whole-body oxygen consumption (VO2) was measured using indirect calorimetry at baseline, at reduced oxygen delivery (DO2) using positive end-expiratory pressure, and at increased DO2 using volume infusion. As a group, no significant increase or decrease in VO2 was observed with changes in DO2. However, 4 patients showed increases in VO2 of 14%, 10.8%, 9.6%, and 8.2% when DO2 was increased. The study results suggest that pathological oxygen supply dependency is present in a subset of patients with CESLD, and the existence of occult tissue ischemia is speculated.

Adult↗
PubMed1999

Clinical use of respiratory changes in arterial pulse pressure to monitor the hemodynamic effects of PEEP.

In ventilated patients with acute lung injury (ALI) we investigated whether respiratory changes in arterial pulse pressure (DeltaPP) could be related to the effects of PEEP and fluid loading (FL) on cardiac index (CI). Measurements were performed before and after application of a PEEP (10 cm H2O) in 14 patients. When the PEEP-induced decrease in CI was > 10% (six patients), measurements were also performed after FL. Maximal (PPmax) and minimal (PPmin) values of pulse pressure were determined over one respiratory cycle and DeltaPP was calculated: DeltaPP (%) = 100 x ((PPmax - PPmin)/ ([PPmax + PPmin]/2)). PEEP decreased CI from 4.2 +/- 1.1 to 3.8 +/- 1.3 L/min/m2 (p < 0.01) and increased DeltaPP from 9 +/- 7 to 16 +/- 13% (p < 0.01). The PEEP-induced changes in CI correlated with DeltaPP on ZEEP (r = -0.91, p < 0.001) and with the PEEP-induced increase in DeltaPP (r = -0.79, p < 0.001). FL increased CI from 3.5 +/- 1.1 to 4.2 +/- 0.9 L/min/m2 (p < 0.05) and decreased DeltaPP from 27 +/- 13 to 14 +/- 9% (p < 0.05). The FL-induced changes in CI correlated with DeltaPP before FL (r = 0.97, p < 0.01) and with the FL-induced decrease in DeltaPP (r = -0.85, p < 0.05). In ventilated patients with ALI, DeltaPP may be useful in predicting and assessing the hemodynamic effects of PEEP and FL.

Adult↗
PubMed1999

Effects of norepinephrine on the renal vasculature in normal and endotoxemic dogs.

Septic shock is often complicated by systemic hypotension despite normal or increased cardiac output. Restoration of arterial pressure usually requires the administration of systemic vasopressor agents, such as norepinephrine. However, because norepinephrine induces vasoconstriction in other vascular beds, it may decrease visceral blood flow, impairing visceral organ function. Because sepsis is often associated with impaired peripheral vascular responsiveness, we hypothesized that, unlike in normal circulatory conditions, norepinephrine would improve visceral organ blood flow in sepsis by selectively increasing organ perfusion pressure. Thus, in nine pentobarbital-anesthetized, mechanically ventilated dogs, we measured the effect of norepinephrine infusion (0.3 microgram/kg/min) on renal, hepatic, and portal steady-state pressure-flow relations (P/Q) and the dynamic vascular P/Q, created by transient inferior vena caval occlusion, under basal and endotoxic conditions. Norepinephrine increased organ perfusion pressures during both control and endotoxemic conditions. However, even after controlling for the pressure effect using a general linear model, NE was associated with an increase in renal blood flow both before and after endotoxin administration. We conclude that, unlike the effects of administering norepinephrine under baseline conditions, norepinephrine infusion during endotoxic shock actually increases renal blood flow and that this effect is not the result of an increase in perfusion pressure alone.

Animals↗
PubMed1999

Determinants of aortic pressure variation during positive-pressure ventilation in man.

STUDY OBJECTIVES: To define the relation between systolic arterial pressure (SAP) changes during ventilation and left ventricular (LV) performance in humans. DESIGN: Prospective repeat-measures series. SETTING: University of Pittsburgh Medical Center Operating Room. PATIENTS: Fifteen anesthetized cardiac surgery patients before and after cardiopulmonary bypass when the mediastinum was either closed or open. INTERVENTIONS: Positive-pressure ventilation. MEASUREMENTS AND RESULTS: SAP and LV midaxis cross-sectional areas were measured during apnea and then were measured for three consecutive breaths. SAP increased during inspiration, this being the greatest during closed chest conditions (p < 0.05). Changes in SAP could not be correlated with changes in either LV end-diastolic areas (EDAs), end-systolic areas, or stroke areas (SAs). If SAP decreased relative to apnea, the decrease occurred during expiration and was often associated with increasing LV EDAs and SAs. SAP often decreased after a positive-pressure breath, but the decrease was unrelated to SA deficits during the breath. Increases in SAP were in phase with increases in airway pressure, whereas decreases in SAP, if present, followed inspiration. No consistent relation between SAP variation and LV area could be identified. CONCLUSIONS: In this patient group, changes in SAP reflect changes in airway pressure and (by inference) intrathoracic pressure (as in a Valsalva maneuver) better than they reflect concomitant changes in LV hemodynamics.

Aorta↗
PubMed1998

Assessment of left ventricular contractile state by preload-adjusted maximal power using echocardiographic automated border detection.

OBJECTIVES: We sought to assess the ability of preload-adjusted maximal power measured by echocardiographic automated border detection (ABD) to quantify left ventricular (LV) contractility by determining the effects of alterations in preload, afterload and contractile state. BACKGROUND: Preload-adjusted maximal power can reflect LV contractile state relatively independent of changes in loading conditions. METHODS: Eight anesthetized dogs had placement of aortic electromagnetic flow probes, LV and arterial pressure catheters and inferior vena caval (IVC) occluders; four had placement of thoracic aortic balloon occluders. Echocardiographic ABD measures of cross-sectional area were used as a surrogate for LV volume, and flow was estimated as the first derivative of area with respect to time. Power was calculated as the product of flow and pressure. RESULTS: Preload independence during vena caval occlusions was achieved by preload adjustment (1/[end-diastolic area]3/2). Afterload independence was demonstrated by preload-adjusted maximal power being unaffected by acute increases in LV systolic pressure induced by aortic occlusion. ABD preload-adjusted maximal power reflected changes in contractile state: increasing with dobutamine infusion from 36+/-14 to 70+/-15 mW/cm4 (p < 0.05 vs. control) and decreasing with propranolol infusion from 35+/-13 to 17+/-7 mW/cm4 (p < 0.05 vs. control). These changes were significantly correlated with calculations of preload-adjusted maximal power using aortic flow (r = 0.90, SEE 10.5 mW/cm4) and load-independent measures of end-systolic elastance from pressure-area loops (r = 0.90, SEE 10.6 mW/cm4). Calculations of normalized preload-adjusted maximal power using arterial pressure were also closely correlated with similar calculations using LV pressure (r = 0.99, SEE 3%). CONCLUSIONS: Preload-adjusted maximal power using echocardiographic ABD can predict LV contractile state relatively independent of loading conditions and has potential for clinical application.

Animals↗
PubMed1998

The American-European Consensus Conference on ARDS, part 2. Ventilatory, pharmacologic, supportive therapy, study design strategies and issues related to recovery and remodeling.

The acute respiratory distress syndrome (ARDS) continues as a contributor to the morbidity and mortality of patients in intensive care units throughout the world, imparting tremendous human and financial costs. During the last ten years there has been a decline in ARDS mortality without a clear explanation. The American-European Consensus Committee on ARDS was formed to re-evaluate the standards for the ICU care of patients with acute lung injury (ALI), with regard to ventilatory strategies, the more promising pharmacologic agents, and the definition and quantification of pathological features of ALI that require resolution. It was felt that the definition of strategies for the clinical design and coordination of studies between centers and continents was becoming increasingly important to facilitate the study of various new therapies for ARDS.

Americas↗
PubMed1998

Occult nitric oxide inhalation improves oxygenation in mechanically ventilated children.

OBJECTIVES: Auto-inhalation of nitric oxide (NO) produced in the upper airways may have physiologic effects on lung function. For intubated patients, the upper airway source of NO is eliminated, but the hospital compressed air source from the environment is contaminated with varying levels of NO, creating an "occult" form of NO therapy. We examined the physiologic significance of occult inhaled NO in ventilator-dependent pediatric patients. We hypothesized that very low levels of NO contamination in inspired gas improve PaO2 in ventilator-dependent children. STUDY DESIGN: Inspired NO levels at the mouth were measured by chemiluminescence in 4 pediatric subjects with normal lungs and 3 with parenchymal lung disease. Subjects were sequentially ventilated with first standard hospital gas (H1), switched to pure nitrogen-oxygen at a similar FIO2 but with no NO contamination (A2), hospital gas again (H2), the nitrogen-oxygen (A2) to control for time and sequence, and finally the nitrogen-oxygen mixture with supplemental NO in an amount equal to the NO previously measured in hospital gas (A2 + NO). Inhaled NO levels and PaO2 were recorded 15 minutes into each of the 5 steps. Two patients were studied a second time, remote from their first examination. RESULTS: NO levels in inhaled hospital gas mixtures ranged from 13 to 79 ppb (mean H1 = 53.3 +/- 23.7 ppb, mean H2 = 53.2 +/- 20.7 ppb, mean A2 + NO = 45 +/- 15.3 ppb; P < .0001). Removing NO from ventilator gas decreased PaO2 in all subjects, whereas replacing NO in artificial gas restored PaO2 to baseline values (P < .0001). CONCLUSION: Concentrations of NO in hospital compressed air are variable and have physiologic effects. The long-term implications of these findings remain to be defined.

Child↗
PubMed1998

Diffusive vs. convective therapy: effects on mediators of inflammation in patient with severe systemic inflammatory response syndrome.

OBJECTIVE: To compare two forms of continuous renal replacement therapy, continuous venovenous hemofiltration (CVVH) vs. continuous venovenous hemodialysis (CVVHD), in terms of the removal of inflammatory mediators from the blood of patients with systemic inflammatory response syndrome and acute renal failure. DESIGN: Randomized crossover, clinical study. SETTING: University teaching hospital. PATIENTS: Thirteen patients with systemic inflammatory response syndrome and acute renal failure receiving continuous renal replacement therapy. INTERVENTION: Patients were randomized to receive either convective clearance using CVVH or diffusive clearance using CVVHD for the first 24 hrs, followed by the other modality for 24 hrs. All treatments utilized AN69 hemofilters. CVVH was performed with an ultrafiltration rate of 2 L/hr and CVVHD with a dialysis outflow rate of 2 L/hr. MEASUREMENTS AND MAIN RESULTS: Plasma and ultrafiltrate concentrations of tumor necrosis factor (TNF)-alpha, interleukin (IL)-6, IL-10, and sL-selectin were measured at 0, 1, 3, 6, 12, and 24 hrs by radioimmunoassay. Plasma endotoxin concentrations were also measured at 0, 12, and 24 hrs by chromogenic assay. CVVH was associated with a 13% decrease in plasma TNF-alpha concentrations compared with a 23% increase while on CVVHD (p < .05). Mean plasma concentrations of IL-6, IL-10, and sL-selectin were unchanged over time and between therapies. Only minimal amounts of mediators were recovered in the effluents with either therapy except for IL-6. The clearances for IL-6 were different between therapies, 1.9+/-0.8 (SD) mL/min for CVVHD and 3.3+/-1.5 mL/min for CVVH, (p< .01). Plasma endotoxin concentrations were not different between therapies. CONCLUSION: CVVH resulted in a decrease in plasma TNF-alpha concentrations as compared with CVVHD, while the type of transport mechanism used did not influence plasma concentrations of IL-6, IL-10, soluble L-selectin, or endotoxin. Differences in clearance for IL-6 between CVVH and CVVHD did not translate into significant changes in circulating IL-6 concentrations.

Acute Kidney Injury↗
PubMed1998

Nitric oxide production after acute, unilateral hydrochloric acid-induced lung injury in a canine model.

OBJECTIVE: To determine if acute unilateral lung injury induces only local or systemic inflammatory effects by measuring the production of nitric oxide (NO) and its metabolites (nitrites and nitrates) in the injured and the contralateral lung and the blood initially and 4 hrs after injury. DESIGN: Unilateral hydrochloric acid instillation in split lung intubated subject studied over time. SETTING: Animal physiology laboratory. SUBJECTS: Five mongrel dogs. INTERVENTIONS: Instillation of 10 mL of 0.1 N hydrochloric acid into one lung via a plastic catheter. Bronchoalveolar lavage (BAL) was done at 4 hrs. MEASUREMENTS AND MAIN RESULTS: Unilateral acid instillation did not alter systemic blood pressure or cardiac output, nor did it induce arterial hypoxemia. The BAL nitrite and nitrate level on the side of injury was higher than the control side (3.6+/-1.36 vs. 1.5+/-1.58 mM, p < .05), and serum nitrites and nitrates levels also decreased from the levels before acid instillation levels (p < .05). Exhaled NO levels were measured only in three animals. The levels increased acutely on hydrochloric acid instillation from only the injured lung and returned to baseline over several minutes. However, the level of exhaled NO from the injured lung failed to increase 4 hrs after injury, despite the increase in BAL nitrites and nitrates. CONCLUSIONS: Acute unilateral lung injury in the dog results in increased NO production that is compartmentalized to the injured lung. The increase in exhaled NO after injury is transient and does not allow one to monitor the progress of lung injury.

Animals↗
PubMed1998

Etiology of metabolic acidosis during saline resuscitation in endotoxemia.

We sought to understand the mechanism of metabolic acidosis that results in acute resuscitated endotoxic shock. In six pentobarbital-anesthetized dogs, shock was induced by Escherichia coli endotoxin infusion (1 mg/kg) and was treated with saline infusion to maintain mean arterial pressure > 80 mmHg. Blood gases and strong ions were measured during control conditions and at 15, 45, 90, and 180 min after endotoxin infusion. The mean saline requirement was 1833+/-523 mL over a 3 h period. The total acid load from each source was calculated using the standard base deficit. The mean arterial pH decreased from 7.32 to 7.11 (p < .01); pCO2 and lactate were unchanged. Saline accounted for 42% of the total acid load. However, 52% of the total acid load was unexplained. Although serum Na+ did not change, serum Cl-increased (127.7+/-5.1 mmol/L vs. 137.0+/-6.1 mmol/L; p=.016). We conclude that saline resuscitation alone accounts for more than one-third of the acidosis seen in this canine model of acute endotoxemia, whereas lactate accounts for less than 10%. A large amount of the acid load can be attributed to differential Na+ and Cl- shifts from extravascular to vascular spaces.

Acidosis↗
PubMed1998

The American-European Consensus Conference on ARDS, part 2: Ventilatory, pharmacologic, supportive therapy, study design strategies, and issues related to recovery and remodeling. Acute respiratory distress syndrome.

The acute respiratory distress syndrome (ARDS) continues as a contributor to the morbidity and mortality of patients in intensive care units throughout the world, imparting tremendous human and financial costs. During the last 10 years there has been a decline in ARDS mortality without a clear explanation. The American-European Consensus Committee on ARDS was formed to re-evaluate the standards for the ICU care of patients with acute lung injury (ALI), with regard to ventilatory strategies, the more promising pharmacologic agents, and the definition and quantification of pathologic features of ALI that require resolution. It was felt that the definition of strategies for the clinical design and coordination of studies between centers and continents was becoming increasingly important to facilitate the study of various new therapies for ARDS.

Europe↗
PubMed1998

Measuring resource use in the ICU with computerized therapeutic intervention scoring system-based data.

BACKGROUND AND OBJECTIVE: In this era of health-care reform, there is increasing need to monitor and control health-care resource consumption. This requires the development of measurement tools that are practical, uniform, reproducible, and of sufficient detail to allow comparison among institutions, among select groups of patients, and among individual patients. We explored the feasibility of generating an index of resource use based on the Therapeutic Intervention Scoring System (TISS) from hospital electronic billing data. Such an index is potentially comparable across institutions, allows assessment of care at many levels, is well understood by clinicians, and captures many of the resources relevant to the ICU. DESIGN: We developed an automated mapping of the hospital billing database into the different items of TISS and generated computerized active TISS scores on 1,372 ICU days. The computerized score was then validated by comparison to prospectively gathered active TISS scores by trained data collectors. SETTING: Eight ICUs within a university teaching institution. PATIENTS: We studied 1,229 general medical and surgical ICU patients. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Active TISS scores ranged from 0 to 31 points. The two scores were well correlated (R2=0.53) and highly calibrated (as assessed by regression of active TISS on mean computerized active TISS [R2=0.85]). The scores were identical on 756 days (55.6%) and differed by < or = 3 TISS points on an additional 387 (28.2%) days. Interreliability assessment suggested substantial agreement (kappa statistic=0.71). The discriminatory power of the computerized score to identify different levels of ICU resource use was excellent as assessed by area under the receiver operating characteristics curves at four threshold points (0.91, 0.87, 0.89, and 0.88). Performance of the computerized score was similar across medical, coronary, and surgical ICU patient groups. CONCLUSION: An automated algorithm can reproduce valid TISS scores from standard hospital billing data, allowing comparison of patients and groups of patients in order to better understand ICU resource use.

Accounting↗
PubMed1998

Controlled observations in critical care medicine: the therapeutic trial.

The practice of critical care medicine revolves around the monitoring of patients to identify acute physiologic deterioration and the titration of therapies aimed at supporting internal homeostasis. Central to this practice is the evaluation of therapies or stresses designed to assess homeostatic reserve and to uncover pathologic processes. Both the cardiovascular and respiratory systems have received particular attention because of the ease with which specific haemodynamic and respiratory parameters can be measured, the ability to modulate their status with therapies, and the intimacy of both cardiovascular and respiratory status to overall homeostasis. These forms of assessment are referred to as clinical trials, and if performed in a rigorous fashion are referred to as controlled clinical trials. Clinical trials form much of the basis for titration of therapy, wherein a specific therapy is adjusted so as to optimise its effectiveness in an individual. Titration is typically done once a diagnosis has already been made or a treatment identified, such as with the titration of antihypertensive therapy in either hospital or outpatient setting. This review will focus on the exploratory aspect of clinical trials wherein a specific manoeuvre is performed to determine either the aetiology or severity of a pathophysiologic problem.

Cardiovascular Diseases↗
PubMed1997

Quantitative assessment of alterations in regional left ventricular contractility with color-coded tissue Doppler echocardiography. Comparison with sonomicrometry and pressure-volume relations.

BACKGROUND: Tissue Doppler imaging (TDI) is a novel method of color-coding myocardial velocity on-line. The objective of the present study was to evaluate endocardial velocity with TDI as a method of objectively quantifying alterations in regional contractility over a wide range induced by inotropic modulation. METHODS AND RESULTS: Myocardial length crystals were used to simultaneously assess regional left ventricular (LV) function, and high-fidelity pressure and conductance catheters were used to assess global LV contractility by pressure-volume relations in nine open-chest dogs. Mid-LV M-mode and two-dimensional color TDI images were recorded during control and inotropic modulation stages with dobutamine and esmolol. Predicted significant increases in TDI indices occurred with dobutamine: peak systolic velocity of 4.41 +/- 1.07 to 6.67 +/- 1.07 cm/s*, systolic time-velocity integral (TVI) of 0.43 +/- 0.12 to 0.62 +/- 0.10 cm*, and diastolic TVI of 0.49 +/- 0.11 to 0.71 +/- 0.17 cm*. Opposing significant decreases occurred with esmolol: peak systolic velocity of 4.46 +/- 0.94 to 2.31 +/- 0.81 cm/s*, systolic TVI of 0.47 +/- 0.12 to 0.19 +/- 0.11 cm*, and diastolic TVI of 0.55 +/- 0.11 to 0.33 +/- 0.11 cm* (*all P < .001 versus control). Changes in TDI peak systolic velocity were correlated with changes in fractional shortening (r = .88) and shortening velocity (r = .87) by sonomicrometry. Changes in TDI peak velocity from multiple mid-LV sites also correlated significantly with maximal elastance (r = .85 +/- .04) from pressure-volume relations. CONCLUSIONS: TDI measures reflect directional and incremental alterations in regional and global LV contractility and have the potential to quantify regional LV function.

Adrenergic beta-Antagonists↗