Charles R. Blocher

A proposed relationship between increased intra-abdominal, intrathoracic, and intracranial pressure.

OBJECTIVES To determine the effect of acutely increased intra-abdominal pressure on pleural pressure, intracranial pressure, and cerebral perfusion pressure, and to clarify the relationship between these parameters. DESIGN Nonrandomized, controlled study. SETTING Laboratory at a university medical center. SUBJECTS Yorkshire swine, weighing 15 to 20 kg. INTERVENTIONS Anesthetized, ventilated swine had a balloon inserted into the peritoneal cavity and catheters placed for measurement of intracranial pressure, pleural pressure, central venous pressure, pulmonary artery occlusion pressure, and mean arterial pressure. Following baseline measurements, intra-abdominal pressure was increased by incrementally inflating the intraperitoneal balloon. All parameters were remeasured 30 mins after each increase in intra-abdominal pressure. Two groups were studied: a) group 1 (n = 9) animals had intra-abdominal pressure increased to 25 mm Hg above baseline, then released; b) group 2 (n = 3) animals underwent sternotomy and pleuropericardotomy to prevent an increase in pleural pressure with increasing intra-abdominal pressure. MEASUREMENTS AND MAIN RESULTS Increase of intra-abdominal pressure to 25 mm Hg above baseline caused significant (p < .05) increases in intracranial pressure (7.3 +/- 0.6 [SEM] to 16.4 +/- 1.9 mm Hg), pleural pressure (4.3 +/- 1.3 to 11.8 +/- 1.9 mm Hg), pulmonary artery occlusion pressure (9.0 +/- 0.6 to 14.3 +/- 0.8 mm Hg), and central venous pressure (6.6 +/- 0.7 to 10.7 +/- 0.9 mm Hg). The cardiac index (3.4 +/- 0.3 to 1.6 +/- 0.1 L/min/m2) and cerebral perfusion pressure (75.6 +/- 3.6 to 62.0 +/- 6.8 mm Hg) deceased significantly (p < .05), whereas mean arterial pressure (82.8 +/- 3.2 to 78.4 +/- 6.6 mm Hg) remained essentially constant. Sternotomy and pleuro-pericardotomy negated all effects of increased intra-abdominal pressure except the decreased cardiac index (1.6 +/- 0.1 to 2.5 +/- 0.2 L/min/m2). CONCLUSIONS Acutely increased intra-abdominal pressure causes a significant increase in intracranial pressure and a decrease in cerebral perfusion pressure. Increased intra-abdominal pressure appears to produce this effect by augmenting pleural and other intrathoracic pressures and causing a functional obstruction to cerebral venous outflow via the jugular venous system. It is possible that the same phenomenon may be why persons with chronically increased intra-abdominal pressure, such as the morbidly obese, suffer from a high frequency rate of idiopathic intracranial hypertension.

Cardiopulmonary effects of raised intra-abdominal pressure before and after intravascular volume expansion.

The cardiopulmonary effects of acutely elevated intra-abdominal pressure (IAP) were studied in a porcine model to help define more clearly IAP effects in patients with trauma. IAP was increased in six anesthetized swine by intra-abdominal instillation of isotonic ethylene glycol up to an IAP of 25 mm Hg above baseline. Systemic and pulmonary hemodynamic parameters were measured, as well as the effects on bladder pressure, pleural pressure, and pulmonary function. At IAP of 25 mm Hg above baseline, intravascular volume expansion with saline was administered to return the cardiac index (CI) to baseline. Raising IAP correlated with measured bladder pressures (r = 0.9, p = 0.001). At IAP of 25 mm Hg, CI was significantly decreased (p < 0.05, analysis of variance (ANOVA); 3.6 +/- 0.3 vs. 2.2 +/- 0.3 L/min/m2); whereas wedge, pulmonary arterial, and pleural pressures were all elevated (p < 0.05, ANOVA). However, transarterial wedge pressure (wedge--pleural pressure) declined nonsignificantly with increasing IAP. Raised IAP caused impaired pulmonary function with a decreased (p < 0.05, ANOVA) PaO2 and increased (p < 0.05, ANOVA) PaCO2. Despite the elevated wedge pressure, fluid resuscitation returned CI to baseline. These data clarify the hemodynamic changes associated with raised IAP and indicate that care must be taken in interpreting hemodynamic measurements to determine intravascular fluid status in patients with elevated IAP.

Effect of increased renal venous pressure on renal function.

OBJECTIVE Acute renal failure is seen with the acute abdominal compartment syndrome (AACS). Although the cause of acute renal failure in AACS may be multifactorial, renal vein compression alone has not been investigated. This study evaluated the effects of elevated renal vein pressure (RVP) on renal function. METHODS Two groups of swine (18-22 kg) were studied after left nephrectomy and placement of a renal artery flow probe to measure renal artery blood flow, renal vein catheter, and ureteral cannula. Two hours were allowed for equilibration and an inulin infusion was begun to calculate inulin clearance for measurement of glomerular filtration rate. Group 1 animals (n = 4) had RVP elevated by 30 mm Hg for 2 hours with renal vein constriction. RVP was then returned to baseline for 1 hour. In group 2 (n = 4), the RVP was not elevated. The cardiac index (2.9 +/- 0.5 L/min/m2) and mean arterial pressure (101 +/- 9 mm Hg) remained stable. Plasma renin activity and serum aldosterone were measured every 60 minutes. RESULTS Elevation of RVP (0-30 mm Hg above baseline) in the experimental group showed a significant decrease in renal artery blood flow index (2.7 to 1.5 mL/min per g) and glomerular filtration rate (26 to 8 mL/min) compared with control. In addition, there was significant elevation of plasma serum aldosterone (14 to 25 microng/dL) and plasma renin activity (2.6 to 9.5 microng/mL per h) as well as urinary protein leak in the experimental animals compared with control. These changes were partially or completely reversible as RVP returned toward baseline. CONCLUSION Elevated RVP alone leads to decreased renal artery blood flow and glomerular filtration rate and increased plasma renin activity, serum aldosterone, and urinary protein leak. These changes are consistent with the renal pathophysiology seen in AACS, morbid obesity, and preeclampsia. The changes are partially or completely reversed by decreasing renal venous pressure as occurs with abdominal decompression for AACS.

Elevated Intra-abdominal Pressure Increases Plasma Renin Activity and Aldosterone Levels

OBJECTIVE To study the effects of elevated intra-abdominal pressure upon renal function and the renin-angiotensin-aldosterone system. MATERIALS AND METHODS Two groups of anesthetized, ventilated swine were studied. Intra-abdominal pressure was increased in experimental animals (n = 6) by incrementally instilling an isosmotic ethylene glycol solution into the peritoneal cavity until intra-abdominal pressure was 25 mm Hg above baseline. The intravascular volume was then expanded until cardiac index returned to baseline. Lastly, the solution was drained to decompress the abdomen. Control animals underwent surgical preparation but did not have their intra-abdominal pressure raised. Changes in systemic and pulmonary hemodynamic parameters, renal venous pressure, and urine output were recorded. Venous samples for plasma renin activity, aldosterone, and atrial natriuretic factor were drawn after each change in either intra-abdominal pressure or intravascular volume in experimental animals, and at the same time points in control animals. MEASUREMENTS AND MAIN RESULTS Elevated intra-abdominal pressure significantly (p < 0.05, analysis of variance) increased renal venous pressure, pleural pressure, wedge pressure, and pulmonary artery pressure compared to both baseline and control animals; whereas cardiac index and urine output decreased significantly. Both plasma renin and aldosterone levels increased significantly compared with baseline and controls. Intravascular volume expansion significantly increased urine output and decreased significantly both plasma renin activity and aldosterone levels. Abdominal decompression further significantly decreased both plasma renin activity and aldosterone levels. There were no significant changes in atrial natriuretic factor at any time point. CONCLUSIONS Elevated intra-abdominal pressure decreases urine output and significantly up-regulates the hormonal output of the renin-angiotensin-aldosterone system. Intravascular volume expansion in combination with abdominal decompression reverses the effects of acutely elevated intra-abdominal pressure upon renal function and the renin-angiotensin-aldosterone system.

Effects of increased intra-abdominal pressure upon intracranial and cerebral perfusion pressure before and after volume expansion.

OBJECTIVE To study the effects of elevated intra-abdominal pressure (IAP) upon intracranial (ICP) and cerebral perfusion pressure (CPP) before and after intravascular volume resuscitation. MATERIALS AND METHODS Intra-abdominal pressure was increased in five anesthetized swine by inflating an intraperitoneal balloon until the IAP was 25 mm Hg above baseline. Intravascular volume was then expanded and finally abdominal decompression was performed. Changes in ICP and systemic and pulmonary hemodynamic parameters secondary to increasing IAP were measured. The effect upon CPP was derived from these measurements. PaO2 and PaCO2 were maintained relatively constant by increasing ventilatory rate. MEASUREMENTS AND MAIN RESULTS Elevated IAP significantly increased ICP (7.6 +/- 1.2 vs. 21.4 +/- 1.0), pleural pressure and central venous pressure; whereas cardiac index and CPP (82.2 +/- 6.3 vs. 62.0 +/- 10.0) decreased significantly. Intravascular volume expansion further significantly increased ICP (27.8 +/- 1.0), and significantly increased both mean arterial pressure (83.4 +/- 14.0 versus 103.4 +/- 8.9) and CPP (75.6 +/- 9.0). Abdominal decompression returned ICP (11.2 +/- 1.8) toward baseline and further increased CPP (79.8 +/- 9.7). CONCLUSIONS Elevated IAP increases ICP and decreases CPP and cardiac index. Volume expansion further increases ICP yet improves CPP via its greater positive effect upon mean arterial pressure (*p < 0.05, analysis of variance. All measurements are mean +/- SEM in mm Hg).

Pretreatment with inhaled nitric oxide inhibits neutrophil migration and oxidative activity resulting in attenuated sepsis-induced acute lung injury

OBJECTIVE To determine if, and by what mechanisms, inhaled nitric oxide attenuates acute lung injury in a porcine model of adult respiratory distress syndrome induced by Gram-negative sepsis. DESIGN Nonrandomized, controlled study. SETTING Laboratory at a university medical center. SUBJECTS Thirty pathogen-free Yorkshire swine (15 to 20 kg). INTERVENTIONS Four groups of swine were anesthetized, mechanically ventilated, and studied for 5 hrs. Both control-nitric oxide and septic-nitric oxide animals received inhaled nitric oxide at 20 parts per million throughout the study. Control (n = 10) and control-nitric oxide (n = 5) animals received a 1-hr infusion of sterile saline. Sepsis was induced in septic (n = 10) and septic-nitric oxide (n = 5) animals with a 1-hr intravenous infusion of live Pseudomonas aeruginosa. MEASUREMENTS AND MAIN RESULTS Untreated septic animals developed a progressive decrease in Pao2 that was prevented in septic-nitric oxide animals (73 +/- 4 vs. 214 +/- 23 torr [9.7 +/- 0.5 vs. 28.5 +/- 3.1 kPa], respectively, at 5 hrs, p < .05). Untreated septic animals showed a significant increase in bronchoalveolar lavage protein and neutrophil count at 5 hrs, compared with the baseline value, indicating acute lung injury. Septic-nitric oxide animals showed no significant increase in these parameters. Peripheral blood neutrophils from untreated septic animals and septic-nitric oxide animals exhibited significant (p < .05) up-regulation of CD18 receptor expression and oxidant activity (10.5 +/- 0.9 and 5.0 +/- 0.9 nmol of superoxide anion/10(6) neutrophils/10 mins, respectively) compared with both control and control-nitric oxide animals (3.0 +/- 0.6 and 2.6 +/- 0.2 nmol of superoxide anion/10(6) neutrophils/10 mins, respectively). Also, priming for the oxidant burst at 5 hrs was decreased by 50% in septic-nitric oxide animals compared with untreated septic animals. Both untreated septic and septic-nitric oxide animals showed a significant increase in pulmonary arterial pressure at 30 mins (47.5 +/- 2.4 and 51.0 +/- 3.0 mm Hg, respectively), followed by a progressive decrease (32.8 +/- 2.6 and 31.3 +/- 5.4 mm Hg, respectively, at 5 hrs). Both of these changes were significant (p < .05) compared with baseline values and compared with the control groups. There was no significant difference in pulmonary arterial pressure or systemic arterial pressure at any time between untreated septic and septic-nitric oxide animals. CONCLUSIONS These results demonstrate that inhaled nitric oxide attenuates alveolar-capillary membrane injury in this porcine model of Gram-negative sepsis but does not adversely affect systemic hemodynamics. The data suggest that inhaled nitric oxide preserves alveolar-capillary membrane integrity by the following means: a) inhibiting transendothelial migration of activated, tightly adherent neutrophils; and b) possibly by attenuating the neutrophil oxidant burst.

Effects of Increased Renal Parenchymal Pressure on Renal Function

OBJECTIVE Acute renal failure is seen with the acute abdominal compartment syndrome (AACS). The cause of acute renal failure in AACS is thought to be multifactorial, including increased renal venous pressure, renal parenchymal pressure (RPP), and decreased cardiac output. Previous studies have established the role of renal venous pressure as an important mediator of this renal derangement. In this study, we evaluate the role of renal parenchymal compression on renal function. METHODS Two groups of swine (20-26 kg) were studied after left nephrectomy and placement of a renal artery flow probe and ureteral cannula. Two hours were allowed for equilibration, and an inulin infusion was begun to calculate inulin clearance as a measurement of glomerular filtration. In group 1 animals (n = 6), RPP was elevated by 30 mm Hg for 2 hours with renal parenchymal compression. RPP then returned to baseline for 1 hour. In group 2 (n = 6), the RPP was not elevated. The cardiac index, preload, and mean arterial pressure remained stable. Blood samples for plasma renin activity and plasma aldosterone were taken at baseline and at hourly intervals. RESULTS Elevation of RPP in the experimental group showed no significant decrease in renal blood flow index or glomerular filtration when compared with control animals. There were no significant elevations of plasma aldosterone or plasma renin activity in the experimental animals when compared with control. CONCLUSION Elevated renal compression alone did not create the pathophysiologic derangements seen in AACS. However, prior data from this laboratory found that renal vein compression alone caused a decreased renal blood flow and glomerular filtration and an increased plasma renin activity, plasma aldosterone, and urinary protein leak. These changes are partially or completely reversed by decreasing renal venous pressure as occurs with abdominal decompression for AACS. These data strengthen the proposal that renal vein compression, and not renal parenchymal compression, is the primary mediator of the renal derangements seen in AACS.

Physiologic effects of externally applied continuous negative abdominal pressure for intra-abdominal hypertension.

BACKGROUND To determine the ability of an externally applied continuous negative abdominal pressure device (CNAP) to reverse the effects of elevated intra-abdominal pressure on the central nervous and cardiovascular systems. METHODS Anesthetized, ventilated swine had catheters placed for measurement of intra-abdominal (IAP), intracranial (ICP), central venous, pulmonary artery, pulmonary artery occlusion, mean arterial, peak inspiratory, inferior vena cava, and femoral vein pressures. After the animals stabilized, baseline measurements were obtained. IAP was increased by incrementally instilling an isosmotic polyethylene glycol solution into the peritoneal cavity until it was 25 mm Hg above baseline. IAP was maintained at 25 mm Hg above baseline for 2 hours. CNAP was then applied for 2 hours. All parameters were remeasured 30 minutes after each increase in IAP, at 2 hours after attaining maximum IAP, and lastly at 2 hours after abdominal decompression. Cardiac index was maintained near baseline by volume expansion. RESULTS Elevation of IAP to 25 mm Hg above baseline for 2 hours caused increases (p<0.05) in central venous pressure (10.3+/-0.9 to 15.2+/-1.7), inferior vena cava pressure (13.0+/-1.0 to 29.5+/-1.5), femoral vein pressure (13.5+/-0.5 to 33.3+/-1.3), ICP (10.6+/-1.5 to 21.0+/-1.5), and peak inspiratory pressure (18.3+/-0.3 to 34.2+/-1.0). The mean arterial pressure (106.3+/-3.5 to 125.8+/-3.4), pulmonary artery pressure (24.3+/-2.3 to 31.3+/-1.7), and pulmonary artery occlusion pressure rose (12.3+/-0.9 to 17.5+/-3.5), but not significantly. Cardiac index (3.3+/-0.5 to 3.4+/-0.4) remained essentially unchanged. CNAP significantly (p<0.05) decreased IAP (30.7+/-1.3 to 18.2+/-1.3), central venous pressure (15.2+/-1.7 to 12.4+/-2.1), inferior vena cava (29.5+/-1.5 to 19.2+/-1.3), and ICP (21.0+/-1.5 to 16.2+/-1.3). Pulmonary artery occlusion pressure (17.5+/-3.5 to 15.0+/-3.1) and peak inspiratory pressure (34.2+/-1.0 to 29.7+/-1.1) decreased, but not significantly. CONCLUSION Acutely elevated IAP causes a significant increase in ICP and impaired cardiovascular and pulmonary function. Abdominal decompression remains the standard of care for abdominal compartment syndrome. However, in patients in whom an increased IAP does not require surgical decompression, the results of this study suggest that externally applied CNAP may be of value.

Amplified cytokine response and lung injury by sequential hemorrhagic shock and abdominal compartment syndrome in a laboratory model of ischemia-reperfusion.

BACKGROUND Increased intra-abdominal pressure has been shown to result in a myriad of physiologic aberrations that result in the abdominal compartment syndrome (ACS). The clinically relevant combination of hemorrhagic shock and resuscitation and subsequent ACS, however, has not been studied in detail. We hypothesized that sequential hemorrhagic shock (HS) and ACS would result in greater cytokine activation and polymorphonuclear neutrophil (PMN)-mediated lung injury than with either insult alone. METHODS Twenty Yorkshire swine (20-30 kg) were studied. Group 1 (n = 5) was hemorrhaged to a mean arterial pressure of 25 to 30 mm Hg for 60 minutes and resuscitated to baseline mean arterial pressure. Intra-abdominal pressure was then increased to 30 mm Hg above baseline and maintained for 60 minutes. Group 2 (n = 5) was subjected to HS alone and Group 3 (n = 5) to ACS alone. Group 4 (n = 5) had sham experiment without HS or ACS. Central and portal venous interleukin-1beta, interleukin-8, and tumor necrosis factor-alpha levels were serially measured. Bronchoalveolar lavage (BAL) for protein and PMNs was performed at baseline and 24 hours after resuscitation. Lung myeloperoxidase was evaluated at 24 hours after resuscitation. RESULTS Portal and central vein cytokine levels were equivalent but were significantly higher in Group 1 than in other groups. BAL PMNs were higher (p < 0.05) in Group 1 (4.1 +/- 2.0 x 106) than in the other groups (0.6 +/- 0.5, 1.4 +/- 1.3, and 0.1 +/- 0.0 x 106, respectively) and lung myeloperoxidase activity was higher (p < 0.05) in Group 1 (134.6 +/- 57.6 x 106/g) than in the other groups (40.3 +/- 14.7, 46.1 +/- 22.4, and 7.73 +/- 4.4 x 106/g, respectively). BAL protein was higher (p < 0.01) in Group 1 (0.92 +/- 0.32 mg/mL) compared with the other groups (0.22 +/- 0.08, 0.29 +/- 0.11, and 0.08 +/- 0.06 mg/mL, respectively). CONCLUSION In this clinically relevant model, sequential insults of ischemia-reperfusion (HS and resuscitation) and ACS were associated with significantly increased portal and central venous cytokine levels and more severe lung injury than HS or ACS alone.

The effects of hemodynamic shock and increased intra-abdominal pressure on bacterial translocation.

BACKGROUND We hypothesized that hemorrhagic shock followed by the abdominal compartment syndrome (ACS) resulted in bacterial translocation (BT) from the gastrointestinal (GI) tract. METHODS Nineteen Yorkshire swine (20-30 kg) were divided into two groups. In the experimental group, group 1 (n = 10), animals were hemorrhaged to a mean arterial pressure (MAP) of 25-30 mm Hg for a period of 30 minutes and resuscitated to baseline MAP. Subsequently, intra-abdominal pressure (IAP) was increased to 30 mm Hg above baseline by instilling sterile normal saline into the peritoneal cavity. The IAP was maintained at this level for 60 minutes. Acid/base status, gastric mucosal ph (pHi), superior mesenteric artery (SMA) blood flow, and hemodynamic parameters were measured and recorded. Blood samples were analyzed by polymerase chain reaction (PCR) for the presence of bacteria. Spleen, lymph node, and portal venous blood cultures were obtained at 24 hours. Results were analyzed by ANOVA and are reported as mean +/- SEM. The second group was the control. These animals did not have the hemorrhage, resuscitation, or intra-abdominal hypertension (IAH) but were otherwise similar to the experimental group in terms of laparotomy and measured parameters. RESULTS SMA blood flow in group 1 (baseline of 0.87 +/- 0.10 l/min) decreased in response to hemorrhage (0.53 +/- 0.10 l/min, p = 0.0001) and remained decreased with IAH (0.63 l/min +/- 0.10, p = 0.0006) as compared to control and returned towards baseline (1.01 +/- 0.5 l/min) on relief of IAH. pHi (baseline of 7.21 +/- 0.03) was significantly decreased with hemorrhage (7.04 +/- 0.03, p = 0.0003) and decreased further after IAH (6.99 +/- 0.03, p = 0.0001) in group 1 compared to control, but returned toward baseline at 24 hours (7.28 +/- 0.04). The mean arterial pH decreased significantly from 7.43 +/- 0.01 at baseline to 7.27 +/- 0.01 at its nadir within group 1 (p = 0.0001) as well as when compared to control (p = 0.0001). Base excess was also significantly decreased between groups 1 and 2 during hemorrhage (3.30 +/- 0.71 vs. 0.06 +/- 0.60, p = 0.001) and IAH (3.08 +/- 0.71 vs. -1.17 +/- 0.60, p = 0.0001). In group 1, 8 of the 10 animals had positive lymph node cultures, 2 of the 10 had positive spleen cultures, and 2 of the 10 had positive portal venous blood cultures for gram-negative enteric bacteria. Only 2 of the 10 animals had a positive PCR. In group 2, five of the nine animals had positive lymph node cultures, zero of the nine had positive spleen cultures, and one of the nine had positive portal venous blood cultures. Two of the nine animals had positive PCRs. There was no significant difference in cultures or PCR results between the two groups (Fishers exact test, p = 0.3). CONCLUSION In this study, hemorrhage followed by reperfusion and a subsequent insult of IAH caused significant GI mucosal acidosis, hypoperfusion, as well as systemic acidosis. These changes did not appear to be associated with a significant bacterial translocation as judged by PCR measurements, tissue, or blood cultures.