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.

The great fluid debate: saline or so-called "balanced" salt solutions?

BACKGROUND Intravenous fluids are commonly prescribed in childhood. 0.9 % saline is the most-used fluid in pediatrics as resuscitation or maintenance solution. Experimental studies and observations in adults suggest that 0.9 % saline is a poor candidate for fluid resuscitation. Although anesthesiologists, intensive care specialists, perioperative physicians and nephrologists have been the most active in this debate, this issue deserves some physiopathological considerations also among pediatricians. RESULTS As compared with so-called "balanced" salt crystalloids such as lactated Ringer, administration of large volumes of 0.9 % saline has been associated with following deleterious effects: tendency to hyperchloremic metabolic acidosis (called dilution acidosis); acute kidney injury with reduced urine output and salt retention; damaged vascular permeability and stiffness, increase in proinflammatory mediators; detrimental effect on coagulation with tendency to blood loss; detrimental gastrointestinal perfusion and function; possible uneasiness at the bedside resulting in unnecessary administration of more fluids. Nevertheless, there is no firm evidence that these adverse effects are clinically relevant. CONCLUSIONS Intravenous fluid therapy is a medicine like insulin, chemotherapy or antibiotics. Prescribing fluids should fit the child's history and condition, consider the right dose at the right rate as well as the electrolyte levels and other laboratory variables. It is unlikely that a single type of fluid will be suitable for all pediatric patients. "Balanced" salt crystalloids, although more expensive, should be preferred for volume resuscitation, maintenance and perioperatively. Lactated Ringer appears unsuitable for patients at risk for brain edema and for those with overt or latent chloride-deficiency. Finally, in pediatrics there is a need for new fluids to be developed on the basis of a better understanding of the physiology and to be tested in well-designed trials.

Retrospective study of salinomycin toxicosis in 66 cats

We examined 66 cats with salinomycin intoxication. Salinomycin caused different LMN signs of varying degrees of severity in all cases. Changes in blood work were unspecific, with the most frequent being increased serum creatine kinase activity, leukocytosis, and increased liver enzymes. Pathological electrodiagnostic findings: fibrillation potentials and positive sharp waves were detected in 10 cases, motor nerve conductance velocity was mildly decreased in 8/12 cats, and sensory nerve conductance velocity and repetitive nerve stimulation were normal in all examined cases. In five cases the peripheral neuropathy was confirmed by pathohistology. Fluid therapy and supportive care were used as therapy and 52 cats recovered completely. The probability for complete remission was significantly different between mildly and severely affected cases. It seems that the severity of clinical signs and prognosis correlate well with the amount of toxin ingested. We conclude that early recognition and decontamination combined with supportive care results in complete recovery.

Ischemic muscle necrosis leading to life-threatening hyperkalemia. Case report and review of the literature

Objective: Description of a cat with ischemic muscle necrosis that suffered from cardiopulmonary arrest due to hyperkalemia. Pathogenesis, clinical signs and therapy of ischemic muscle necrosis are discussed and possible causes, symptoms and treatment of hyperkalemia are shown. Material and methods: case report of a four-year-old male castrated domestic shorthair cat. Results: The cat was successfully resuscitated and hyperkalemia was treated with different treatment modalities. Conclusion: Ischemic muscle necrosis can lead to severe live-threatening hyperkalemia which has to be anticipated, monitored and treated adequately. Aggressive fluid therapy might be responsible for a higher risk of hyperkalemia in predisposed cases. Clinical relevance: Potassium concentrations and acid-base disturbances must be closely monitored in patients with ischemic muscle necrosis

Pulmonary capillary pressure. A review

Pulmonary capillary pressure (Pcap) is the predominant force that drives fluid out of the pulmonary capillaries into the interstitium. Increasing hydrostatic capillary pressure is directly proportional to the lung's transvascular filtration rate, and in the extreme leads to pulmonary edema. In the pulmonary circulation, blood flow arises from the transpulmonary pressure gradient, defined as the difference between pulmonary artery (diastolic) pressure and left atrial pressure. The resistance across the pulmonary vasculature consists of arterial and venous components, which interact with the capacitance of the compliant pulmonary capillaries. In pathological states such as acute respiratory distress syndrome, sepsis, and high altitude or neurogenic lung edema, the longitudinal distribution of the precapillary arterial and the postcapillary venous resistance varies. Subsequently, the relationship between Pcap and pulmonary artery occlusion pressure (PAOP) is greatly variable and Pcap can no longer be predicted from PAOP. In clinical practice, PAOP is commonly used to guide fluid therapy, and Pcap as a hemodynamic target is rarely assessed. This approach is potentially misleading. In the presence of a normal PAOP and an increased pressure gradient between Pcap and PAOP, the tendency for fluid leakage in the capillaries and subsequent edema development may substantially be underestimated. Tho-roughly validated methods have been developed to assess Pcap in humans. At the bedside, measurement of Pcap can easily be determined by analyzing a pressure transient after an acute pulmonary artery occlusion with the balloon of a Swan-Ganz catheter.

Monitoring eines Hundes mit traumatischem Hämoabdomen durch serielle Messung von abdominalem und peripher venösem Hämatokrit

Objective: This case report describes the use of serial measurements of peripheral venous and abdominal fluid hematocrits as a guide to treatment in a dog with traumatic hemoabdomen. Material and methods: An 18-month-old, female mixed-breed dog was presented with traumatic hemoabdomen. The dog was treated with intravenous fluids, and concurrent measurements of venous and abdominal fluid hematocrits were performed. Results: The initial hematocrit values were 39% in venous blood and 42% in abdominal fluid. Following fluid therapy, the venous hematocrit decreased to 20%, whereas the abdominal hematocrit remained stable at 40%. Based on this finding severe ongoing intra-abdominal hemorrhage was ruled out, and the dog was treated conservatively. Conclusion and clinical relevance: Comparison of serial abdominal and venous hematocrits may be useful in assessing the need for surgical management in patients with traumatic hemoabdomen.

Goal-directed colloid administration improves the microcirculation of healthy and perianastomotic colon

BACKGROUND: The aim of this study was to compare the effects of goal-directed colloid fluid therapy with goal-directed crystalloid and restricted crystalloid fluid therapy on healthy and perianastomotic colon tissue in a pig model of colon anastomosis surgery. METHODS: Pigs (n = 27, 9 per group) were anesthetized and mechanically ventilated. A hand-sewn colon anastomosis was performed. The animals were subsequently randomized to one of the following treatments: R-RL group, 3 ml x kg(-1) x h(-1) Ringer lactate (RL); GD-RL group, 3 ml x kg(-1) x h(-1) RL + bolus 250 ml of RL; GD-C group, 3 ml x kg(-1) x h(-1) RL + bolus 250 ml of hydroxyethyl starch (HES 6%, 130/0.4). A fluid bolus was administered when mixed venous oxygen saturation dropped below 60%. Intestinal tissue oxygen tension and microcirculatory blood flow were measured continuously. RESULTS: After 4 h of treatment, tissue oxygen tension in healthy colon increased to 150 +/- 31% in group GD-C versus 123 +/- 40% in group GD-RL versus 94 +/- 23% in group R-RL (percent of postoperative baseline values, mean +/- SD; P < 0.01). Similarly perianastomotic tissue oxygen tension increased to 245 +/- 93% in the GD-C group versus 147 +/- 58% in the GD-RL group and 116 +/- 22% in the R-RL group (P < 0.01). Microcirculatory flow was higher in group GD-C in healthy colon. CONCLUSIONS: Goal-directed colloid fluid therapy significantly increased microcirculatory blood flow and tissue oxygen tension in healthy and injured colon compared to goal-directed or restricted crystalloid fluid therapy.

Evaluation of the Hepa Wash® treatment in pigs with acute liver failure

BACKGROUND Mortality of patients with acute liver failure (ALF) is still unacceptably high. Available liver support systems are still of limited success at improving survival. A new type of albumin dialysis, the Hepa Wash® system, was newly introduced. We evaluated the new liver support system as well as the Molecular Adsorbent Recycling System (MARS) in an ischemic porcine model of ALF. METHODS In the first study animals were randomly allocated to control (n=5) and Hepa Wash (n=6) groups. In a further pilot study, two animals were treated with the MARS-system. All animals received the same medical and surgical procedures. An intraparenchymal intracranial pressure was inserted. Hemodynamic monitoring and goal-directed fluid therapy using the PiCCO system was done. Animals underwent functional end-to-side portacaval shunt and ligation of hepatic arteries. Treatment with albumin dialysis was started after fall of cerebral perfusion pressure to 45 mmHg and continued for 8 h. RESULTS All animals in the Hepa Wash group survived the 13-hour observation period, except for one that died after stopping treatment. Four of the control animals died within this period (p=0.03). Hepa Wash significantly reduced impairment of cerebral perfusion pressure (23±2 vs. 10±3 mmHg, p=0.006) and mean arterial pressure (37±1 vs. 24±2 mmHg, p=0.006) but had no effect on intracranial pressure (14±1 vs. 15±1 mmHg, p=0.72). Hepa Wash also enhanced cardiac index (4.94±0.32 vs. 3.36±0.25 l/min/m2, p=0.006) and renal function (urine production, 1850 ± 570 vs. 420 ± 180 ml, p=0.045) and eliminated water soluble (creatinine, 1.3±0.2 vs. 3.2±0.3 mg/dl, p=0.01; ammonia 562±124 vs. 1382±92 μg/dl, p=0.006) and protein-bound toxins (nitrate/nitrite 5.54±1.57 vs. 49.82±13.27 μmol/l, p=0.01). No adverse events that could be attributed to the Hepa Wash treatment were observed. CONCLUSIONS Hepa Wash was a safe procedure and improved multiorgan system failure in pigs with ALF. The survival benefit could be the result of ameliorating different organ functions in association with the detoxification capacity of water soluble and protein-bound toxins.

Retrospective evaluation of the effects of administration of tetrastarch (hydroxyethyl starch 130/0.4) on plasma creatinine concentration in dogs (2010-2013): 201 dogs

OBJECTIVE To determine changes in creatinine concentrations following the administration of 6% tetrastarch (hydroxyethyl starch [HES] 130/0.4) compared to crystalloids (CRYSs) in critically ill dogs. DESIGN Retrospective case series (2010-2013). SETTING University teaching hospital. ANIMALS Two hundred and one dogs admitted to the intensive care unit with initial plasma creatinine concentrations not exceeding laboratory reference intervals (52-117 μmol/L [0.6-1.3 mg/dL]) and receiving either CRYSs alone (CRYS group, n = 115) or HES with or without CRYSs (HES group, n = 86) for at least 24 hours. INTERVENTIONS None. MEASUREMENTS AND MAIN RESULTS Creatinine concentrations at admission to the intensive care unit (T0), and 2-13 days (T1) and 2-12 weeks (T2) after initiation of fluid therapy were analyzed. Creatinine concentrations were analyzed as absolute values and as the maximum percentage change from T0 to T1 (T1max%) and from T0 to T2 (T2max%), respectively. Creatinine concentrations were available for 192 dogs during T1 and 37 dogs during T2. The median cumulative dose of HES was 86 mL/kg (range, 12-336 mL/kg). No difference was detected between the groups for age, gender, body weight, and length of hospitalization. Outcome was significantly different between the HES (66% survived) and the CRYS (87% survived) groups (P = 0.014). No significant difference was detected between groups for creatinine concentrations at T0, T1, T2, T1max%, or T2max%. No significant difference was detected between the groups for T1max% creatinine in dogs subclassified as having systemic inflammatory response syndrome or sepsis. CONCLUSIONS HES administration in this canine population did not result in increased creatinine concentrations compared to administration of CRYSs. Further studies are needed to establish the safety of HES in critically ill dogs.

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.

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.

Higher CNS Penetration-Effectiveness of Long-term Combination Antiretroviral Therapy Is Associated With Better HIV-1 Viral Suppression in Cerebrospinal Fluid

Objectives: To determine HIV-1 RNA in cerebrospinal fluid (CSF) of successfully treated patients and to evaluate if combination antiretroviral treatments with higher central nervous system penetration-effectiveness (CPE) achieve better CSF viral suppression. Methods: Viral loads (VLs) and drug concentrations of lopinavir, atazanavir, and efavirenz were measured in plasma and CSF. The CPE was calculated using 2 different methods. Results: The authors analyzed 87 CSF samples of 60 patients. In 4 CSF samples, HIV-1 RNA was detectable with 43–82 copies per milliliter. Median CPE in patients with detectable CSF VL was significantly lower compared with individuals with undetectable VL: CPE of 1.0 (range, 1.0–1.5) versus 2.3 (range, 1.0–3.5) using the method of 2008 (P = 0.011) and CPE of 6 (range, 6–8) versus 8 (range, 5–12) using the method of 2010 (P = 0.022). The extrapolated CSF trough levels for atazanavir (n = 12) were clearly above the 50% inhibitory concentration (IC50) in only 25% of samples; both patients on atazanavir/ritonavir with detectable CSF HIV-1 RNA had trough levels in the range of the presumed IC50. The extrapolated CSF trough level for lopinavir (n = 42) and efavirenz (n = 18) were above the IC50 in 98% and 78%, respectively, of samples, including the patients with detectable CSF HIV-1 RNA. Conclusions: This study suggests that treatment regimens with high intracerebral efficacy reflected by a high CPE score are essential to achieve CSF HIV-1 RNA suppression. The CPE score including all drug components was a better predictor for treatment failure in the CSF than the sole concentrations of protease inhibitor or nonnucleoside reverse transcriptase inhibitor in plasma or CSF.

Effect of nonsurgical periodontal treatment in conjunction with either systemic administration of amoxicillin and metronidazole or additional photodynamic therapy on the concentration of matrix metalloproteinases 8 and 9 in gingival crevicular fluid in patients with aggressive periodontitis.

BACKGROUND To evaluate in patients with aggressive periodontitis (AgP) the effect of nonsurgical periodontal treatment in conjunction with either additional administration of systemic antibiotics (AB) or application of photodynamic therapy (PDT) on the gingival crevicular fluid (GCF) concentration of matrix metalloproteinases 8 and 9 (MMP-8 and -9). METHODS Thirty-six patients with AgP were included in the study. Patients were randomly assigned to treatment with either scaling and root planing (SRP) followed by systemic administration of AB (e.g. Amoxicillin + Metronidazole) or SRP + PDT. The analysis of MMP-8 and -9 GCF concentrations was performed at baseline and at 3 and 6 months after treatment. Nonparametric U-Mann-Whitney test was used for comparison between groups. Changes from baseline to 3 and 6 months were analyzed with the Friedman's ANOVA test with Kendall's index of consistency. RESULTS In the AB group, patients showed a statistically significant (p = 0.01) decrease of MMP-8 GCF level at both 3 and 6 months post treatment. In the PDT group, the change of MMP-8 GCF level was not statistically significant. Both groups showed at 3 and 6 months a decrease in MMP-9 levels. However, this change did not reach statistical significance. CONCLUSIONS Within the limits of the present study, it may be suggested that in patients with AgP, nonsurgical periodontal therapy in conjunction with adjunctive systemic administration of amoxicilin and metronidazole is more effective in reducing GCF MMP-8 levels compared to the adjunctive use of PDT.

Comparison of gingival crevicular fluid sampling methods in patients with severe chronic periodontitis

The analysis of samplings from periodontal pockets is important in the diagnosis and therapy of periodontitis. In this study, three different sampling techniques were compared to determine whether one method yielded samples suitable for the reproducible and simultaneous determination of bacterial load, cytokines, neutrophil elastase, and arginine-specific gingipains (Rgps). Rgps are an important virulence factor of Porphyromonas gingivalis, the exact concentration of which in gingival crevicular fluid (GCF) has not been quantified.