Relationship between ocular perfusion pressure and retrobulbar blood flow in patients with glaucoma with progressive damage

PURPOSE: To evaluate the relationship between ocular perfusion pressure and color Doppler measurements in patients with glaucoma. MATERIALS AND METHODS: Twenty patients with primary open-angle glaucoma with visual field deterioration in spite of an intraocular pressure lowered below 21 mm Hg, 20 age-matched patients with glaucoma with stable visual fields, and 20 age-matched healthy controls were recruited. After a 20-minute rest in a supine position, intraocular pressure and color Doppler measurements parameters of the ophthalmic artery and the central retinal artery were obtained. Correlations between mean ocular perfusion pressure and color Doppler measurements parameters were determined. RESULTS: Patients with glaucoma showed a higher intraocular pressure (P <.0008) and a lower mean ocular perfusion pressure (P <.0045) compared with healthy subjects. Patients with deteriorating glaucoma showed a lower mean blood pressure (P =.033) and a lower end diastolic velocity in the central retinal artery (P =.0093) compared with normals. Mean ocular perfusion pressure correlated positively with end diastolic velocity in the ophthalmic artery (R = 0.66, P =.002) and central retinal artery (R = 0.74, P <.0001) and negatively with resistivity index in the ophthalmic artery (R = -0.70, P =.001) and central retinal artery (R = -0.62, P =.003) in patients with deteriorating glaucoma. Such correlations did not occur in patients with glaucoma with stable visual fields or in normal subjects. The correlations were statistically significantly different between the study groups (parallelism of regression lines in an analysis of covariance model) for end diastolic velocity (P =.001) and resistivity index (P =.0001) in the ophthalmic artery, as well as for end diastolic velocity (P =.0009) and resistivity index (P =. 001) in the central retinal artery. CONCLUSIONS: The present findings suggest that alterations in ocular blood flow regulation may contribute to the progression in glaucomatous damage.

An optimized model for rat liver perfusion studies

Conditions which influence the viability, integrity, and extraction efficiency of the isolated perfused rat liver were examined to establish optimal conditions for subsequent work in reperfusion injury studies including the choice of buffer, use of oncotic agents, hematocrit, perfusion flow rate, and pressure. Rat livers were perfused with MOPS-buffered Ringer solution with or without erythrocytes. Perfusates were collected and analyzed for blood gases, electrolytes, enzymes, radioactivity in MID studies, and lignocaine in extraction studies. Liver tissue was sampled for histological examinations, and wet:dry weight of the liver was also determined. MOPS-buffered Ringer solution was found to be superior to Krebs bicarbonate buffer, in terms of pH control and buffering capacity, especially during any prolonged period of liver perfusion. A pH of 7.2 is chosen for perfusion since this is the physiological pH of the portal blood. The presence of albumin was important as an oncotic agent, particularly when erythrocytes were used in the perfusate. Perfusion pressure, resistance, and vascular volume are how-dependent and the inclusion of erythrocytes in the perfusate substantially altered the flow characteristics for perfusion pressure and resistance but not vascular volume. Lignocaine extraction was relatively flow-independent. Perfusion injury as defined by enzyme release and tissue fine structure was closely related to the supply of O-2. The optimal conditions for liver perfusion depend upon an adequate supply of oxygen. This can be achieved by using either erythrocyte-free perfusate at a how rate greater than 6 ml/min/g liver or a 20% erythrocyte-containing perfusate at 2 ml/min/g. (C) 1996 Academic Press, Inc.

Low Hematocrit Levels Increase Intracranial Pressure in an Animal Model of Cryogenic Brain Injury

Background: Brain injury is responsible for significant morbidity and mortality in trauma patients, but controversy still exists over optimal fluid management for these patients. This study aimed to investigate the effects of acute hemodilution with hydroxyethyl starch (HES) or lactated Ringer`s solution (LR) in intracranial pressure (ICP) and cerebral perfusion pressure (CPP) in dogs submitted to a cryogenic brain injury model. Methods: Design-Prospective laboratory animal study. Setting-Research laboratory in a teaching hospital. Subjects-Thirty-five male mongrel dogs. Interventions-Animals were enrolled to five groups: control, hemodilution with LR or HES 6% to an hematocrit target of 27% or 35%. Results: ICP and CPP levels were measured after cryogenic brain injury. Hemodilution promotes an increment of ICP levels, which decreases CPP when hematocrit target was estimated in 27.% after hemodilution. However, no differences were observed regarding crystalloid or colloid solution used for hemodilution in ICP and CPP levels. Conclusions: Hemodilution to a low hematocrit level increases ICP and decreases CPP scores in dogs submitted to a cryogenic brain injury. These results suggest that excessive hemodilution to a hematocrit below 30% should be avoided in traumatic brain injury patients.

Ethanol consumption increases blood pressure and alters the responsiveness of the mesenteric vasculature in rats

Chronic ethanol Consumption and hypertension are related. In the current study we investigated whether changes in reactivity of the mesenteric arterial bed could account for the increased blood pressure associated with chronic ethanol intake. Changes in reactivity to phenylephrine and acetylcholine were investigated in the perfused mesenteric bed from rats treated with ethanol for 2 or 6 weeks and their age-matched controls. Mild hypertension was observed in chronically ethanol-treated rats. Treatment of rats for 6 weeks induced an increase in the contractile response of endothelium-intact mesenteric bed to phenylephrine, but not denuded rat mesenteric bed. The phenylephrine-induced increase in perfusion pressure was not altered after 2 weeks` treatment with ethanol. Moreover, acetylcholine-induced endothelium-dependent relaxation was reduced by ethanol treatment for 6 weeks, but not 2 weeks. Pre-treatment with indometacin, a cyclooxygenase inhibitor, reduced the maximum effect induced by phenylephrine (E-max) in endothelium-intact mesenteric bed from both control and ethanol-treated rats. No differences in the E-max values for phenylephrine were observed between groups in the presence of indometacin. L-NNA, a nitric oxide (NO) synthase (NOS) inhibitor, increased the E-max for phenylephrine in endothelium-intact mesenteric bed from control rats but not from ethanol-treated rats. Levels of endothelial NOS (eNOS) mRNA were not altered by chronic ethanol consumption. However, chronic ethanol intake strongly reduced eNOS protein levels in the mesenteric bed. This study shows that chronic ethanol consumption increases blood pressure and alters the reactivity of the mesenteric bed. Moreover, the increased vascular response to phenylephrine observed in the mesenteric bed is maintained by two mechanisms: an increased release of endothelial-derived vasoconstrictor prostanoids and a reduced modulatory action of endothelial NO, which seems to be associated with reduced post-transcriptional expression of eNOS.

Subendocardial fibrosis in remote myocardium results from reduction of coronary driving pressure during acute infarction in rats

OBJECTIVE: To investigate the role of hemodynamic changes occurring during acute MI in subsequent fibrosis deposition within non-MI. METHODS: By using the rat model of MI, 3 groups of 7 rats each [sham, SMI (MI <30%), and LMI (MI >30%)] were compared. Systemic and left ventricular (LV) hemodynamics were recorded 10 minutes before and after coronary artery ligature. Collagen volume fraction (CVF) was calculated in picrosirius red-stained heart tissue sections 4 weeks later. RESULTS: Before surgery, all hemodynamic variables were comparable among groups. After surgery, LV end-diastolic pressure increased and coronary driving pressure decreased significantly in the LMI compared with the sham group. LV dP/dt max and dP/dt min of both the SMI and LMI groups were statistically different from those of the sham group. CVF within non-MI interventricular septum and right ventricle did not differ between each MI group and the sham group. Otherwise, subendocardial (SE) CVF was statistically greater in the LMI group. SE CVF correlated negatively with post-MI systemic blood pressure and coronary driving pressure, and positively with post-MI LV dP/dt min. Stepwise regression analysis identified post-MI coronary driving pressure as an independent predictor of SE CVF. CONCLUSION: LV remodeling in rats with MI is characterized by predominant SE collagen deposition in non-MI and results from a reduction in myocardial perfusion pressure occurring early on in the setting of MI.

Continuous monitoring of cerebrovascular pressure reactivity in patients with head injury.

OBJECT: Cerebrovascular pressure reactivity is the ability of cerebral vessels to respond to changes in transmural pressure. A cerebrovascular pressure reactivity index (PRx) can be determined as the moving correlation coefficient between mean intracranial pressure (ICP) and mean arterial blood pressure. METHODS: The authors analyzed a database consisting of 398 patients with head injuries who underwent continuous monitoring of cerebrovascular pressure reactivity. In 298 patients, the PRx was compared with a transcranial Doppler ultrasonography assessment of cerebrovascular autoregulation (the mean index [Mx]), in 17 patients with the PET-assessed static rate of autoregulation, and in 22 patients with the cerebral metabolic rate for O(2). Patient outcome was assessed 6 months after injury. RESULTS: There was a positive and significant association between the PRx and Mx (R(2) = 0.36, p < 0.001) and with the static rate of autoregulation (R(2) = 0.31, p = 0.02). A PRx > 0.35 was associated with a high mortality rate (> 50%). The PRx showed significant deterioration in refractory intracranial hypertension, was correlated with outcome, and was able to differentiate patients with good outcome, moderate disability, severe disability, and death. The graph of PRx compared with cerebral perfusion pressure (CPP) indicated a U-shaped curve, suggesting that too low and too high CPP was associated with a disturbance in pressure reactivity. Such an optimal CPP was confirmed in individual cases and a greater difference between current and optimal CPP was associated with worse outcome (for patients who, on average, were treated below optimal CPP [R(2) = 0.53, p < 0.001] and for patients whose mean CPP was above optimal CPP [R(2) = -0.40, p < 0.05]). Following decompressive craniectomy, pressure reactivity initially worsened (median -0.03 [interquartile range -0.13 to 0.06] to 0.14 [interquartile range 0.12-0.22]; p < 0.01) and improved in the later postoperative course. After therapeutic hypothermia, in 17 (70.8%) of 24 patients in whom rewarming exceeded the brain temperature threshold of 37 degrees C, ICP remained stable, but the average PRx increased to 0.32 (p < 0.0001), indicating significant derangement in cerebrovascular reactivity. CONCLUSIONS: The PRx is a secondary index derived from changes in ICP and arterial blood pressure and can be used as a surrogate marker of cerebrovascular impairment. In view of an autoregulation-guided CPP therapy, a continuous determination of a PRx is feasible, but its value has to be evaluated in a prospective controlled trial.

Dynamic arterial elastance to predict arterial pressure response to volume loading in preload-dependent patients

INTRODUCTION Hemodynamic resuscitation should be aimed at achieving not only adequate cardiac output but also sufficient mean arterial pressure (MAP) to guarantee adequate tissue perfusion pressure. Since the arterial pressure response to volume expansion (VE) depends on arterial tone, knowing whether a patient is preload-dependent provides only a partial solution to the problem. The objective of this study was to assess the ability of a functional evaluation of arterial tone by dynamic arterial elastance (Ea(dyn)), defined as the pulse pressure variation (PPV) to stroke volume variation (SVV) ratio, to predict the hemodynamic response in MAP to fluid administration in hypotensive, preload-dependent patients with acute circulatory failure. METHODS We performed a prospective clinical study in an adult medical/surgical intensive care unit in a tertiary care teaching hospital, including 25 patients with controlled mechanical ventilation who were monitored with the Vigileo(®) monitor, for whom the decision to give fluids was made because of the presence of acute circulatory failure, including arterial hypotension (MAP ≤65 mmHg or systolic arterial pressure <90 mmHg) and preserved preload responsiveness condition, defined as a SVV value ≥10%. RESULTS Before fluid infusion, Ea(dyn) was significantly different between MAP responders (MAP increase ≥15% after VE) and MAP nonresponders. VE-induced increases in MAP were strongly correlated with baseline Ea(dyn) (r(2) = 0.83; P < 0.0001). The only predictor of MAP increase was Ea(dyn) (area under the curve, 0.986 ± 0.02; 95% confidence interval (CI), 0.84-1). A baseline Ea(dyn) value >0.89 predicted a MAP increase after fluid administration with a sensitivity of 93.75% (95% CI, 69.8%-99.8%) and a specificity of 100% (95% CI, 66.4%-100%). CONCLUSIONS Functional assessment of arterial tone by Ea(dyn), measured as the PVV to SVV ratio, predicted arterial pressure response after volume loading in hypotensive, preload-dependent patients under controlled mechanical ventilation.

Beyond intracranial pressure: optimization of cerebral blood flow, oxygen, and substrate delivery after traumatic brain injury.

Monitoring and management of intracranial pressure (ICP) and cerebral perfusion pressure (CPP) is a standard of care after traumatic brain injury (TBI). However, the pathophysiology of so-called secondary brain injury, i.e., the cascade of potentially deleterious events that occur in the early phase following initial cerebral insult-after TBI, is complex, involving a subtle interplay between cerebral blood flow (CBF), oxygen delivery and utilization, and supply of main cerebral energy substrates (glucose) to the injured brain. Regulation of this interplay depends on the type of injury and may vary individually and over time. In this setting, patient management can be a challenging task, where standard ICP/CPP monitoring may become insufficient to prevent secondary brain injury. Growing clinical evidence demonstrates that so-called multimodal brain monitoring, including brain tissue oxygen (PbtO2), cerebral microdialysis and transcranial Doppler among others, might help to optimize CBF and the delivery of oxygen/energy substrate at the bedside, thereby improving the management of secondary brain injury. Looking beyond ICP and CPP, and applying a multimodal therapeutic approach for the optimization of CBF, oxygen delivery, and brain energy supply may eventually improve overall care of patients with head injury. This review summarizes some of the important pathophysiological determinants of secondary cerebral damage after TBI and discusses novel approaches to optimize CBF and provide adequate oxygen and energy supply to the injured brain using multimodal brain monitoring.

Brain Tissue Hypoxia is a Strong Predictor of Outcome after Severe Traumatic Brain Injury Independent from Elevated Intracranial Pressure

Introduction: Low brain tissue oxygen pressure (PbtO2) is associated with worse outcome in patients with severe traumatic brain injury (TBI). However, it is unclear whether brain tissue hypoxia is merely a marker of injury severity or a predictor of prognosis, independent from intracranial pressure (ICP) and injury severity. Hypothesis: We hypothesized that brain tissue hypoxia was an independent predictor of outcome in patients wih severe TBI, irrespective of elevated ICP and of the severity of cerebral and systemic injury. Methods: This observational study was conducted at the Neurological ICU, Hospital of the University of Pennsylvania, an academic level I trauma center. Patients admitted with severe TBI who had PbtO2 and ICP monitoring were included in the study. PbtO2, ICP, mean arterial pressure (MAP) and cerebral perfusion pressure (CPP = MAP-ICP) were monitored continuously and recorded prospectively every 30 min. Using linear interpolation, duration and cumulative dose (area under the curve, AUC) of brain tissue hypoxia (PbtO2 < 15 mm Hg), elevated ICP >20 mm Hg and low CPP <60 mm Hg were calculated, and the association with outcome at hospital discharge, dichotomized as good (Glasgow Outcome Score [GOS] 4-5) vs. poor (GOS 1-3), was analyzed. Results: A total of 103 consecutive patients, monitored for an average of 5 days, was studied. Brain tissue hypoxia was observed in 66 (64%) patients despite ICP was < 20 mm Hg and CPP > 60 mm Hg (72 +/- 39% and 49 +/- 41% of brain hypoxic time, respectively). Compared with patients with good outcome, those with poor outcome had a longer duration of brain hypoxia (1.7 +/- 3.7 vs. 8.3 +/- 15.9 hrs, P<0.01), as well as a longer duration (11.5 +/- 16.5 vs. 21.6 +/- 29.6 hrs, P=0.03) and a greater cumulative dose (56 +/- 93 vs. 143 +/- 218 mm Hg*hrs, P<0.01) of elevated ICP. By multivariable logistic regression, admission Glasgow Coma Scale (OR, 0.83, 95% CI: 0.70-0.99, P=0.04), Marshall CT score (OR 2.42, 95% CI: 1.42-4.11, P<0.01), APACHE II (OR 1.20, 95% CI: 1.03-1.43, P=0.03), and the duration of brain tissue hypoxia (OR 1.13; 95% CI: 1.01-1.27; P=0.04) were all significantly associated with poor outcome. No independent association was found between the AUC for elevated ICP and outcome (OR 1.01, 95% CI 0.97-1.02, P=0.11) in our prospective cohort. Conclusions: In patients with severe TBI, brain tissue hypoxia is frequent, despite normal ICP and CPP, and is associated with poor outcome, independent of intracranial hypertension and the severity of cerebral and systemic injury. Our findings indicate that PbtO2 is a strong physiologic prognostic marker after TBI. Further study is warranted to examine whether PbtO2-directed therapy improves outcome in severely head-injured patients .

Exercise training prevents increased intraocular pressure and sympathetic vascular modulation in an experimental model of metabolic syndrome

The present study aimed to study the effects of exercise training (ET) performed by rats on a 10-week high-fructose diet on metabolic, hemodynamic, and autonomic changes, as well as intraocular pressure (IOP). Male Wistar rats receiving fructose overload in drinking water (100 g/L) were concomitantly trained on a treadmill for 10 weeks (FT group) or kept sedentary (F group), and a control group (C) was kept in normal laboratory conditions. The metabolic evaluation comprised the Lee index, glycemia, and insulin tolerance test (KITT). Arterial pressure (AP) was measured directly, and systolic AP variability was performed to determine peripheral autonomic modulation. ET attenuated impaired metabolic parameters, AP, IOP, and ocular perfusion pressure (OPP) induced by fructose overload (FT vs F). The increase in peripheral sympathetic modulation in F rats, demonstrated by systolic AP variance and low frequency (LF) band (F: 37±2, 6.6±0.3 vs C: 26±3, 3.6±0.5 mmHg2), was prevented by ET (FT: 29±3, 3.4±0.7 mmHg2). Positive correlations were found between the LF band and right IOP (r=0.57, P=0.01) and left IOP (r=0.64, P=0.003). Negative correlations were noted between KITT values and right IOP (r=-0.55, P=0.01) and left IOP (r=-0.62, P=0.005). ET in rats effectively prevented metabolic abnormalities and AP and IOP increases promoted by a high-fructose diet. In addition, ocular benefits triggered by exercise training were associated with peripheral autonomic improvement.

The effects of 2 levels of the inspired oxygen fraction on blood gas variables in propofol-anesthetized dogs with high intracranial pressure

The influence of 2 different levels of the inspired oxygen fraction (FiO(2)) on blood gas variables was evaluated in dogs with high intracranial pressure (ICP) during propofol anesthesia (induction followed by a continuous rate infusion [CRI] of 0.6 mg/kg/min) and intermittent positive pressure ventilation (IPPV). Eight adult mongrel dogs were anesthetized on 2 occasions, 21 d apart, and received oxygen at an FiO(2) of 1.0 (G100) or 0.6 (G60) in a randomized crossover fashion. A fiberoptic catheter was implanted on the surface of the right cerebral cortex for assessment of the ICP. An increase in the ICP was induced by temporary ligation of the jugular vein 50 min after induction of anesthesia and immediately after baseline measurement of the ICP. Blood gas measurements were taken 20 min later and then at 15-min intervals for 1 h. Numerical data were submitted to Morrison's multivariate statistical methods. The ICP, the cerebral perfusion pressure and the mean arterial pressure did not differ significantly between FiO(2) levels or measurement times after jugular ligation. The only blood gas values that differed significantly (P < 0.05) were the arterial oxygen partial pressure, which was greater with G100 than with G60 throughout the procedure, and the venous haemoglobin saturation, that was greater with G100 than with G60 at M0. There were no significant differences between FiO(2) levels or measurement times in the following blood gas variables: arterial carbon dioxide partial pressure, arterial hemoglobin saturation, base deficit, bicarbonate concentration, pH, venous oxygen partial pressure, venous carbon dioxide partial pressure and the arterial-to-end-tidal carbon dioxide difference.

Bispectral index in dogs with high intracranial pressure, anesthetized with propofol and submitted to two levels of FiO2

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Online correlation of spontaneous arterial and intracranial pressure fluctuations in patients with diffuse severe head injury

Determination of relevant clinical monitoring parameters for helping guide the intensive care therapy in patients with severe head injury, is one of the most demanding issues in neurotrauma research. New insights into cerebral autoregulation and metabolism have revealed that a rigid cerebral perfusion pressure (CPP) regimen might not be suitable for all severe head injured patients. We thus developed an online analysis technique to monitor the correlation (AI rho) between the spontaneous fluctuations of the mean arterial blood pressure (MABP) and the intracranial pressure (ICP). In addition, brain tissue oxygen (PtiO2) and metabolic microdialysate measures including glucose and lactate were registered. We found that in patients with good outcome, the AI rho values were significantly lower as compared with patients with poor outcome. Accordingly, microdialysate glucose and lactate were significantly higher in the good outcome group. We conclude that online determination of AI rho offers a valuable additional and technically easily performable tool for guidance of therapy in patients with severe head injury.

Normobaric hyperoxia--induced improvement in cerebral metabolism and reduction in intracranial pressure in patients with severe head injury: a prospective historical cohort-matched study

OBJECT: The effect of normobaric hyperoxia (fraction of inspired O2 [FIO2] concentration 100%) in the treatment of patients with traumatic brain injury (TBI) remains controversial. The aim of this study was to investigate the effects of normobaric hyperoxia on five cerebral metabolic indices, which have putative prognostic significance following TBI in humans. METHODS: At two independent neurointensive care units, the authors performed a prospective study of 52 patients with severe TBI who were treated for 24 hours with 100% FIO2, starting within 6 hours of admission. Data for these patients were compared with data for a cohort of 112 patients who were treated in the past; patients in the historical control group matched the patients in our study according to their Glasgow Coma Scale scores after resuscitation and their intracranial pressure within the first 8 hours after admission. Patients were monitored with the aid of intracerebral microdialysis and tissue O2 probes. Normobaric hyperoxia treatment resulted in a significant improvement in biochemical markers in the brain compared with the baseline measures for patients treated in our study (patients acting as their own controls) and also compared with findings from the historical control group. In the dialysate the glucose levels increased (369.02 +/- 20.1 micromol/L in the control group and 466.9 +/- 20.39 micromol/L in the 100% O2 group, p = 0.001), whereas the glutamate and lactate levels significantly decreased (p < 0.005). There were also reductions in the lactate/glucose and lactate/pyruvate ratios. Intracranial pressure in the treatment group was reduced significantly both during and after hyperoxia treatment compared with the control groups (15.03 +/- 0.8 mm Hg in the control group and 12.13 +/- 0.75 mm Hg in the 100% O2 group, p < 0.005) with no changes in cerebral perfusion pressure. Outcomes of the patients in the treatment group improved. CONCLUSIONS: The results of the study support the hypothesis that normobaric hyperoxia in patients with severe TBI improves the indices of brain oxidative metabolism. Based on these data further mechanistic studies and a prospective randomized controlled trial are warranted.

Arterial blood pressure during early sepsis and outcome

OBJECTIVE: To evaluate the association between arterial blood pressure (ABP) during the first 24 h and mortality in sepsis. DESIGN: Retrospective cohort study. SETTING: Multidisciplinary intensive care unit (ICU). PATIENTS AND PARTICIPANTS: A total of 274 septic patients. INTERVENTIONS: None. MEASUREMENTS AND RESULTS: Hemodynamic, and laboratory parameters were extracted from a PDMS database. The hourly time integral of ABP drops below clinically relevant systolic arterial pressure (SAP), mean arterial pressure (MAP), and mean perfusion pressure (MPP = MAP - central venous pressure) levels was calculated for the first 24 h after ICU admission and compared with 28-day-mortality. Binary and linear regression models (adjusted for SAPS II as a measure of disease severity), and a receiver operating characteristic (ROC) analysis were applied. The areas under the ROC curve were largest for the hourly time integrals of ABP drops below MAP 60 mmHg (0.779 vs. 0.764 for ABP drops below MAP 55 mmHg; P < or = 0.01) and MPP 45 mmHg. No association between the hourly time integrals of ABP drops below certain SAP levels and mortality was detected. One or more episodes of MAP < 60 mmHg increased the risk of death by 2.96 (CI 95%, 1.06-10.36, P = 0.04). The area under the ROC curve to predict the need for renal replacement therapy was highest for the hourly time integral of ABP drops below MAP 75 mmHg. CONCLUSIONS: A MAP level > or = 60 mmHg may be as safe as higher MAP levels during the first 24 h of ICU therapy in septic patients. A higher MAP may be required to maintain kidney function.