Lactate and glucose concentrations in brain interstitial fluid, cerebrospinal fluid, and serum during experimental pneumococcal meningitis

Metabolic abnormalities during bacterial meningitis include hypoglycorrhachia and cerebrospinal fluid (CSF) lactate accumulation. The mechanisms by which these alterations occur within the central nervous system (CNS) are still incompletely delineated. To determine the evolution of these changes and establish the locus of abnormal metabolism during meningitis, glucose and lactate concentrations in brain interstitial fluid, CSF, and serum were measured simultaneously and sequentially during experimental pneumococcal meningitis in rabbits. Interstitial fluid samples were obtained from the frontal cortex and hippocampus by using in situ brain microdialysis, and serum and CSF were directly sampled. There was an increase of CSF lactate concentration, accompanied by increased local production of lactate in the brain, and a decrease of CSF-to-serum glucose ratio that was paralleled by a decrease in cortical glucose concentration. Brain microdialysate lactate concentration was not affected by either systemic lactic acidosis or artificially elevated CSF lactate concentration. These data support the hypothesis that the brain is a locus for anaerobic glycolysis during meningitis, resulting in increased lactate production and perhaps contributing to decreased tissue glucose concentration.

Effect of hydration status on cerebral blood flow and cerebrospinal fluid lactic acidosis in rabbits with experimental meningitis

The effects of hydration status on cerebral blood flow (CBF) and development of cerebrospinal fluid (CSF) lactic acidosis were evaluated in rabbits with experimental pneumococcal meningitis. As loss of cerebrovascular autoregulation has been previously demonstrated in this model, we reasoned that compromise of intravascular volume might severely affect cerebral perfusion. Furthermore, as acute exacerbation of the inflammatory response in the subarachnoid space has been observed after antibiotic therapy, animals were studied not only while meningitis evolved, but also 4-6 h after treatment with antibiotics to determine whether there would also be an effect on CBF. To produce different levels of hydration, animals were given either 50 ml/kg per 24 h of normal saline ("low fluid") or 150 ml/kg 24 h ("high fluid"). After 16 h of infection, rabbits that were given the lower fluid regimen had lower mean arterial blood pressure (MABP), lower CBF, and higher CSF lactate compared with animals that received the higher fluid regimen. In the first 4-6 h after antibiotic administration, low fluid rabbits had a significant decrease in MABP and CBF compared with, and a significantly greater increase in CSF lactate concentration than, high fluid rabbits. This study suggests that intravascular volume status may be a critical variable in determining CBF and therefore the degree of cerebral ischemia in meningitis.

Influence of granulocytes on brain edema, intracranial pressure, and cerebrospinal fluid concentrations of lactate and protein in experimental meningitis

Brain water content (brain edema), intracranial pressure, and cerebrospinal fluid (CSF) concentrations of lactate and protein increased significantly during 24 h of experimental meningitis due to Streptococcus pneumoniae, but changes were similar in normal and neutropenic rabbits. In sterile meningitis induced by N-formyl-methionyl-leucyl-phenyl-alanine (fMLP), low and high doses of fMLP were equally effective in inducing CSF pleocytosis, whereas only high doses of fMLP caused brain edema. High doses of fMLP injected intracisternally during pneumococcal meningitis also increased brain water content. The fMLP did not significantly increase intracranial pressure or CSF concentrations of lactate or protein in sterile or pneumococcal meningitis, nor did it cause brain edema in neutropenic animals. Thus, granulocytes may contribute to brain edema during meningitis if adequately stimulated, but intracranial pressure and CSF protein and lactate concentrations appear independent of granulocytes. Stimulation does not appear to occur early in meningitis, when granulocytes were without effect on brain edema.

Antibiotic therapy, endotoxin concentration in cerebrospinal fluid, and brain edema in experimental Escherichia coli meningitis in rabbits

We investigated the effect of cefotaxime and chloramphenicol on endotoxin concentrations in cerebrospinal fluid (CSF) and on the development of brain edema in rabbits with Escherichia coli meningitis. Both antibiotics were similarly effective in reducing bacterial titers. Cefotaxime, but not chloramphenicol, induced a marked increase of endotoxin in CSF, from log10 1.5 +/- 0.8 to log10 2.8 +/- 0.7 ng/ml (P less than .01). This result was associated with an increase in brain water content (405 +/- 12 g of water/100 g of dry weight compared with 389 +/- 8 g in untreated controls; P less than .01), whereas in animals treated with chloramphenicol, brain water content was identical to controls. The cefotaxime-induced increase in endotoxin concentration and brain edema were both neutralized by polymyxin B, which binds to the lipid A moiety of endotoxin, or by a monoclonal antibody to lipid A. These results indicate that treating gram-negative bacillary meningitis with selected antibiotics induces increased endotoxin concentrations in CSF that are associated with brain edema.

Effects of ampicillin and corticosteroids on brain water content, cerebrospinal fluid pressure, and cerebrospinal fluid lactate levels in experimental pneumococcal meningitis

A study was made of the effects of antibiotics and corticosteroids on parameters that reflect brain dysfunction and potential neurological damage in experimental pneumococcal meningitis in rabbits. Brain water content was 398 +/- 10 g/100 g dry weight in normal rabbits and 410 +/- 11 g in rabbits after 24 hr of infection (P less than .001). Cerebrospinal fluid (CSF) lactate levels increased from 16.3 +/- 3.4 mg/dl to 69.5 +/- 28.2 mg/dl (P less than .001), and CSF pressure increased by +8.3 +/- 3.6 mm Hg (P less than .005) over the same interval. Antibiotic therapy with ampicillin sterilized CSF and normalized CSF pressure and brain water content in all animals within 24 hr, while CSF lactate levels remained elevated. Administration of methyl prednisolone, 30 mg/kg, or dexamethasone, 1 mg/kg, 15 and 22 hr after infection completely reversed the development of brain edema, but only dexamethasone also significantly reduced the increase in CSF lactate level (43.8 +/- 12.3 mg/dl) and CSF pressure (+1.8 +/- 2.7 mm Hg). Methyl prednisolone did not significantly affect pressure or lactate levels.

The influence of dosing schedules and cerebrospinal fluid bactericidal activity on the therapy of bacterial meningitis

Bacterial meningitis represents an infection in an area of impaired host defence. Optimal therapy of meningitis requires attaining bactericidal activity within cerebrospinal fluid (CSF). Studies in experimental animal models of meningitis suggest that maximal rates of bacterial killing in vivo and optimal cure rates are achieved when CSF antibiotic concentrations exceed the MBC of the test strain by greater than or equal to ten-fold. The results of clinical trials support this conclusion. In addition, a variable post-antibiotic effect occurs in-vivo after short periods of exposure to antimicrobial activity, thus maintaining therapeutic efficacy with intermittent dosage regimens. These basic principles of therapy are outlined in this review and serve as a basis for rational treatment regimens. For most antibiotics, the optimal dose, dosage interval, and duration of therapy for bacterial meningitis remain to be established.

Pharmacodynamics of antibiotics in experimental bacterial meningitis--two sides to rapid bacterial killing in the cerebrospinal fluid

In bacterial meningitis, several pharmacodynamic factors determine therapeutic success--when defined as sterilization of the cerebrospinal fluid (CSF); (i) local host defense deficits require the use of bactericidal antibiotics; (ii) CSF antibiotic concentrations that are at least 10-fold above the MBC are necessary for maximal bactericidal activity; (iii) high CSF peak concentrations that lead to rapid bacterial killing appear more important than prolonged suprainhibitory concentrations, probably because very low residual levels in the CSF prevent bacterial regrowth even during relatively long dosing intervals; (iv) penetration of antibiotics into the CSF is significantly impaired by the blood-brain barrier, thus requiring high serum levels to achieve the CSF concentrations necessary for rapid bacterial killing. Beyond these principles, recent data suggest that rapid lytic killing of bacteria in the CSF may have harmful effects on the brain because of the release of biologically active bacterial products. The conflict between the need for rapid CSF sterilization and the harmful consequences of bacterial lysis must be addressed in the therapy of meningitis.

Fluid percussion injury transiently increases then decreases brain oxygen consumption in the rat

The oxygen consumption (VO2 microL/h/mg) of sham and of traumatized rat brains within 30 min and 6 h after a lateral fluid percussion injury (FPI) was measured with the Cartesian microrespirometer. Brain slices were cut at the plain of injury and site-specific 20-60-microg cores of tissue were transferred to the microrespirometer. In sham brains, the cortical VO2 (CVO2) was 13.78+/-0.64 and the hippocampal VO2 (HPVO2) was 11.20+/-0.58 microL/h/mg (p<0.05). Within 30 min of the injury, the respective values of 16.89+/-0.55 and 14.91+/-0.06 were significantly increased (p<0.05). The combined VO2 (CVO2, HPVO2) of 12.49+/-0.06 microL/h/mg in shams was significantly less than the combined VO2 of 15.90+/-0.59 microL/h/mg at 30 min post FPI (p<0.001). The maximal CVO2 of 19.49+/-1.10 microL/h/mg and the maximal HPVO2 of 15.98+/-0.99 microL/h/mg were both obtained from the ipsilateral side of the injury. Whereas the contralateral cortical value for injured brains was not significantly different from that of the shams, both ipsilateral and contralateral hippocampal values were significantly greater than that of the shams in response to injury (p<0.05). By 6 h postinjury, the combined VO2 had dropped to 10.01+/-0.84 microL/h/mg but was not significantly lower than the sham values. The data indicate that normal CVO2 is greater than normal HPVO2. The FPI produces significant increases in both CVO2 and HPVO2. Also, while the immediate increase in CVO2 appears to be injury-site dependent, that is, regional, the increase in HPVO2 appears to be global.

Crystalloids versus colloids for goal-directed fluid therapy in major surgery

INTRODUCTION: Perioperative hypovolemia arises frequently and contributes to intestinal hypoperfusion and subsequent postoperative complications. Goal-directed fluid therapy might reduce these complications. The aim of this study was to compare the effects of goal-directed administration of crystalloids and colloids on the distribution of systemic, hepatosplanchnic, and microcirculatory (small intestine) blood flow after major abdominal surgery in a clinically relevant pig model. METHODS: Twenty-seven pigs were anesthetized and mechanically ventilated and underwent open laparotomy. They were randomly assigned to one of three treatment groups: the restricted Ringer lactate (R-RL) group (n = 9) received 3 mL/kg per hour of RL, the goal-directed RL (GD-RL) group (n = 9) received 3 mL/kg per hour of RL and intermittent boluses of 250 mL of RL, and the goal-directed colloid (GD-C) group (n = 9) received 3 mL/kg per hour of RL and boluses of 250 mL of 6% hydroxyethyl starch (130/0.4). The latter two groups received a bolus infusion when mixed venous oxygen saturation was below 60% ('lockout' time of 30 minutes). Regional blood flow was measured in the superior mesenteric artery and the celiac trunk. In the small bowel, microcirculatory blood flow was measured using laser Doppler flowmetry. Intestinal tissue oxygen tension was measured with intramural Clark-type electrodes. RESULTS: After 4 hours of treatment, arterial blood pressure, cardiac output, mesenteric artery flow, and mixed oxygen saturation were significantly higher in the GD-C and GD-RL groups than in the R-RL group. Microcirculatory flow in the intestinal mucosa increased by 50% in the GD-C group but remained unchanged in the other two groups. Likewise, tissue oxygen tension in the intestine increased by 30% in the GD-C group but remained unchanged in the GD-RL group and decreased by 18% in the R-RL group. Mesenteric venous glucose concentrations were higher and lactate levels were lower in the GD-C group compared with the two crystalloid groups. CONCLUSIONS: Goal-directed colloid administration markedly increased microcirculatory blood flow in the small intestine and intestinal tissue oxygen tension after abdominal surgery. In contrast, goal-directed crystalloid and restricted crystalloid administrations had no such effects. Additionally, mesenteric venous glucose and lactate concentrations suggest that intestinal cellular substrate levels were higher in the colloid-treated than in the crystalloid-treated animals. These results support the notion that perioperative goal-directed therapy with colloids might be beneficial during major abdominal surgery.

[Arterial pressure curve and fluid status.]

Fluid optimization is a major contributor to improved outcome in patients. Unfortunately, anesthesiologists are often in doubt whether an additional fluid bolus will improve the hemodynamics of the patient or not as excess fluid may even jeopardize the condition. This article discusses physiological concepts of liberal versus restrictive fluid management followed by a discussion on the respective capabilities of various monitors to predict fluid responsiveness. The parameter difference in pulse pressure (dPP), derived from heart-lung interaction in mechanically ventilated patients is discussed in detail. The dPP cutoff value of 13% to predict fluid responsiveness is presented together with several assessment techniques of dPP. Finally, confounding variables on dPP measurements, such as ventilation parameters, pneumoperitoneum and use of norepinephrine are also mentioned.