The therapeutic effect of hypertonic solutions on the changes in the effective circulating plasma volume in acute necrotizing pancreatitis in rats

While hypovolemia or hypovolemic shock is dominant in the early stage of severe acute pancreatitis, there have been few studies on the effects of hypertonic solutions in the management of this disease. We conducted this study to evaluate the therapeutic effects of hypertonic saline solutions (HS) on the course of severe acute pancreatitis in rats. Pancreatitis was induced in male Wistar rats by injecting a 5% solution of sodium taurocholate into the biliopancreatic duct. The effective circulating plasma volume (ECPV) was measured using radioiodinated [125I]bovine serum albumin. Samples of blood and of ascitic fluid were obtained 3, 6, and 12 h after the onset of pancreatitis. Lactated Ringer's solution (LR) and HS were administered consecutively for 3 h beginning 3 h after the induction of pancreatitis. ECPV was measured 6 h after the onset of pancreatitis. The survival rates were investigated for up to 10 days. The mean ECPV decreased significantly from 24.9 +/- 1.1 ml/kg before disease onset to 11.5 +/- 1.3 ml/kg 6 h postoperatively. LR failed to achieve a normal value for ECPV even following a 150 ml/kg infusion. HS200 and HS300 restored the ECPV to the normal level, and with smaller volumes infused. All rats in the untreated group died within 3 days. LR and HS improved the survival rates, with the infusion of HS200, 100 ml/kg, thus attaining a 45% survival at 10 days.     

Diaspirin cross-linked hemoglobin resuscitation improves cerebral perfusion after head injury and shock

BACKGROUND: Shock associated with traumatic brain injury (TBI) doubles the mortality of TBI alone by inducing a secondary ischemic injury. Rapid correction of cerebral perfusion pressure (CPP) is thought to be essential to improving outcome. Diaspirin cross-linked hemoglobin (DCLHb) has been shown to improve cerebral blood flow, increase mean arterial pressure (MAP), and reduce lesion size in models of occlusive cerebral ischemia but has not been evaluated in a model of TBI combined with hemorrhagic shock. METHODS: We studied the effects of DCLHb resuscitation in a porcine model of cryogenic TBI and hemorrhagic shock (MAP = 50 mmHg). After combined insults, animals were randomized to receive a bolus of 4 mliters/kg of either lactated Ringer's solution (n = 5) or DCLHb (n = 6). Lactated Ringer's solution was then infused in both groups to maintain MAP at baseline. Shed blood was returned 1 hour after the initiation of resuscitation (R1). Animals were studied for 24 hours. RESULTS: DCLHb infusion resulted in a significantly greater MAP at R1 and R24 (95 +/- 4 vs. 82 +/- 2 and 99 +/- 3 vs. 85 +/- 3 mm Hg, respectively) and a significantly greater CPP at R1 and R24 (83 +/- 10 vs. 68 +/- 5 and 89 +/- 6 vs. 71 +/- 11 mm Hg, respectively). Intracranial pressure was lower in the DCLHb group, but this difference was not significant. There was no significant difference between the groups in cerebral oxygen delivery. DCLHb animals required less fluid to maintain MAP (12,094 +/- 552 vs. 15,542 +/- 1094 mliters, p < 0.05). CONCLUSION: These data suggest that DCLHb is beneficial in the early resuscitation of head injury and shock and that further investigation is warranted. Key Words: Diaspirin cross-linked hemoglobin, Head injury, Shock, Cerebral perfusion pressure.     

Low-volume resuscitation with a hemoglobin-based oxygen carrier after hemorrhage improves gut microvascular oxygenation in swine

Using palladium-porphyrin quenching of phosphorescence, we investigated the influence of diaspirin cross-linked hemoglobin (DCLHb) on gut microvascular oxygen pressure (microPO2) in anesthetized pigs. Values of gut microPO2 were studied in correlation with regional intestinal as well as global metabolic and circulatory parameters. A controlled hemorrhagic shock (blood withdrawal of 40 mL/kg) was followed by resuscitation with either a combination of lactated Ringer's solution (75 mL/kg) and modified gelatin (15 mL/kg)(lactR/Gel) or 10% DCLHb (5 mL/kg). After resuscitation, gut microPO2 was similarly improved in the lactR/Gel group (from 25 +/- 10 mm Hg to 53 +/- 8 mm Hg) and the DCLHb group (from 23 +/- 9 mm Hg to 46 +/- 6 mm Hg), which was associated with increased gut oxygen delivery. However, the improvement after resuscitation with DCLHb was sustained for longer periods of time (75 vs 30 min). Mesenteric venous PO2 was increased after resuscitation with lactated Ringer's solution and modified gelatin but not with DCLHb, which was associated with an increased gut oxygen consumption in the latter group. We conclude that measurement of microPO2 by the palladium-porphyrin phosphorescence technique revealed DCLHb to be an effective carrier of oxygen to the microcirculation of the gut. Also, this effect can be achieved with a lower volume than is currently used in resuscitation procedures.     

Lactated ringer's is superior to normal saline in a model of massive hemorrhage and resuscitation

BACKGROUND: Previous models comparing normal saline (NS) with lactated Ringer's solution (LR) for resuscitation use only mild or moderate hemorrhage and do not address the clinical situation of massive hemorrhage and resuscitation (MHR). This work compares NS and LR by using a new rat model of MHR. METHODS: NS and LR were compared by using both a traditional model of moderate pressure-controlled hemorrhage and a model of MHR. Moderate hemorrhage animals were bled to mean arterial pressure (MAP) = 60 mm Hg x 2 hour then resuscitated with crystalloid (NS or LR) for 1 hour. MHR animals were bled at a rate of 1 estimated blood volume (EBV) per hour for 2 hours with simultaneous resuscitation by using washed red blood cells (B) and crystalloid (LR+B or NS+B). MAP was kept at 60 mm Hg during the 2 hours of hemorrhage. Bleeding was then stopped, and animals were resuscitated for 1 additional hour with blood and crystalloid to MAP more than 90 mm Hg or until 10x EBV was given. Group means were compared with Student's t test (p < 0.01 significant) and 2-week survival rates were compared by using Fisher's exact test (p < 0.05 significant). RESULTS: The moderate hemorrhage group was bled 36% of EBV. In this setting, resuscitation with NS and LR was equivalent. The final hematocrit, pH, and base excess were not different, and all animals survived in both groups. MHR animals were bled 218% of EBV. Animals resuscitated with NS+B were significantly more acidotic than animals resuscitated with equal volumes of LR+B (pH 7.14+/-.06 vs. 7.39+/-.04, respectively) and had significantly worse survival (50% vs. 100%, respectively). CONCLUSION: With moderate hemorrhage, NS and LR are equivalent, but in the setting of massive hemorrhage and resuscitation, significantly more physiologic derangement and mortality occurs with NS than LR. LR is superior to NS for use in massive resuscitation.     

Uncontrolled hemorrhage from parenchymal injury: is resuscitation helpful?

Fluid resuscitation increases blood pressure and may increase hemorrhage. We tested this hypothesis in a model of liver injury. After standardized injury, rats were randomized into four groups: no resuscitation (NR, n = 30), small volume lactated Ringer's solution (SVLR, 4 mL/kg, n = 30), large volume lactated Ringer's solution (LVLR, 24 mL/kg, n = 30), and hypertonic saline (HS, 4 mL/kg, n = 30). Terminal circulating volume was estimated using controlled hemorrhage experiments. Survival times and mortality rates were significantly lower in HS animals (10%) than in NR (50%) or SVLR (47%) animals. Blood pressure was significantly higher after HS, and this difference was sustained. Intraperitoneal blood volume was significantly higher with HS (26.0 +/- 0.7 mL/kg) and LVLR (26.9 +/- 0.6 mL/kg) compared with NR (21.5 +/- 0.7 mL/kg) and SVLR (22.5 +/- 0.7 mL/kg). Estimated terminal blood volume was significantly decreased in LVLR (29.3 +/- 0.6 mL/kg) compared with NR (33.3 +/- 0.7 mL/kg), SVLR (33.7 +/- 0.8 mL/kg), and HS (31.7 +/- 0.7 mL/kg). CONCLUSION: Vigorous resuscitation increases bleeding from solid viscus injury. Small volume HS improves blood pressure and survival compared with no resuscitation. Results of large vessel hemorrhage models may not apply to parenchymal viscus injury.     

Significant reduction of medical costs by differentiation therapy with all-trans retinoic acid during remission induction of newly diagnosed patients with acute promyelocytic leukemia. The Japan Adult Leukemia Study Group

OBJECTIVE: For resuscitation of hemorrhagic hypovolemia, we compared the effectiveness of (1) isotonic lactated Ringer's solution (LRS), (2) 2400 mOsm of 7.5% NaCl:6% dextran 70 (HSD), and (3) 2400 mOsm of 7.9% sodium acetate:1.9% NaCl:6% dextran 70 (HAD). DESIGN: In six randomized, blinded experiments for each solution, conscious instrumented adult sheep were hemorrhaged by removing approximately 1.8 L (42 +/- 3 mL/kg) of blood, while maintaining the mean arterial pressure (MAP) at 50 mm Hg for 2 hours. METHODS: Test solutions were infused as needed to restore the cardiac index to baseline. RESULTS: Volume requirements with HAD (236 +/- 29 mL) and HSD (244 +/- 39 mL) were significantly less (p < 0.05) than LRS (3463 +/- 234 mL). Mean arterial pressure was normalized with HSD and LRS, but not with HAD, which resulted in MAPs of 20 to 25 mm Hg less than baseline resulting from a reduced peripheral resistance. Oxygen delivery, however, was significantly higher with HAD during the resuscitation period. Acid-base balance (pH) and oxygen consumption were normalized within 5 minutes of infusion only with HAD. CONCLUSIONS: Small-volume infusion with HAD resulting in "high-flow-low-pressure" resuscitation may offer unique hemodynamic and metabolic advantages for the initial treatment of hemorrhage from trauma.     

Effects of glucose load on brain extracellular lactate concentration in conscious rats using a microdialysis technique

Changes in the brain lactate concentration in cerebral extracellular fluid (ECF) during intravenous infusion of glucose and local administration of glucose were investigated in adult, conscious, unrestrained rats, with a microdialysis probe in the posterior hippocampus. The rats were infused intravenously with either 25% sucrose solution or 25% glucose solution at a rate of 16.6 microliters.min-1.100 g-1 for three hours. The blood glucose concentration reached 17.0 +/- 2.6 mM at the end of the glucose infusion, and brain ECF glucose showed a parallel change with the blood glucose concentration and increased to 2.37 +/- 0.30 mM. However, blood and brain ECF glucose concentrations did not change in animals infused with the sucrose solution. On the other hand, the blood lactate concentration in the glucose-infused group also increased from 0.93 +/- 0.18 mM to 2.85 +/- 0.39 mM at the end of the glucose infusion, which was significantly higher than that measured in the sucrose-infused group. The blood lactate level in the glucose-infused group returned to the basal level by the end of the experiment. Brain ECF lactate concentrations increased from 1.21 +/- 0.06 mM to 1.69 +/- 0.11 mM in glucose-infused animals, but did not change in the sucrose-infused animals. The brain ECF lactate concentration showed a positive correlation with the brain ECF glucose concentration in glucose-infused animals. Another group of rats was administered glucose locally for 90 min after substitution of artificial cerebrospinal fluid.(ABSTRACT TRUNCATED AT 250 WORDS)     

Effect of hypertonic saline solution and dextran on ventricular blood flow and heart-lung interaction after hemorrhagic shock

BACKGROUND: Hypertonic saline solutions may have beneficial hemodynamic effects in the resuscitation of hemorrhagic shock. The effects on cardiac function and potential interaction with lung function are controversial and served as the basis for this study. METHODS: Domestic swine were resuscitated from hemorrhagic shock with equivalent sodium loads of lactated Ringer's solution (LR) or 7.5% NaCl plus 10% dextran (HSD). Hemodynamic data were obtained at baseline, shock, and after resuscitation. Right ventricular ejection fraction and left ventricular change in pressure with respect to time (dP/dt) were used to index contractility. Regional myocardial blood flow was determined with microspheres. Lung water was determined gravimetrically. RESULTS: There were no differences in the ability to restore hemodynamic parameters with equivalent sodium loads of LR and HSD resuscitation. Right ventricular ejection fraction and left ventricular change in pressure with respect to time were only transiently affected by shock and resuscitation. Regional myocardial blood flow was increased above baseline values after HSD. The total resuscitation volumes were 1958 +/- 750 mL and 140 +/- 31 mL with LR and HSD, respectively. CONCLUSIONS: Although LR and HSD were equally effective in the early resuscitation of hemorrhagic shock, this occurred at the expense of significantly greater volume requirements for resuscitation with LR. This may contribute to cardiac dysfunction in this setting. Enhanced regional myocardial blood flow after HSD resuscitation may be beneficial against ongoing myocardial stress.     

The efficacy of diaspirin crosslinked hemoglobin solution resuscitation in a model of uncontrolled hemorrhage

Controversy exists whether early aggressive fluid therapy in the setting of uncontrolled hemorrhage worsens outcome by increasing blood loss from injured vessels. Since diaspirin crosslinked hemoglobin (DCLHb) is a vasoactive, oxygen-carrying solution, we compared the effects of DCLHb with other resuscitative fluids on blood loss, hemodynamics, and tissue oxygen delivery in a model of uncontrolled hemorrhage. Anesthetized rats (250-350 g) were subjected to a 50% tail transection and resuscitated 15 minutes later with 1:1 DCLHb, 3:1 lactated Ringer's solution (LR), 1:1 hypertonic saline (7.5% HTS), or 1:1 human serum albumin (8.3% HSA) based on initial volume of blood loss (average 4.7 +/- 0.3 mL/kg). An unresuscitated group served as a control. Cumulative blood loss was measured at 5 hours postresuscitation. By 15 minutes after tail transection, mean arterial pressure (MAP) decreased 19.2 +/- 3.8 mm Hg from the baseline value (102 +/- 5 mm Hg). The DCLHb solution restored and maintained MAP and subcutaneous tissue oxygen tension at baseline values better than all other resuscitative fluids. Although blood loss in DCLHb-treated animals was greater than in unresuscitated animals, it was no different from other resuscitative fluids and less than with HSA. There was no difference in 24-hour survival between all treatment groups. In conclusion, DCLHb elevates MAP but does not exacerbate blood loss or compromise tissue oxygen delivery compared with other resuscitative fluids in this model of uncontrolled hemorrhage.     

Effects of Carolina rinse and adenosine rinse on microvascular perfusion and intrahepatic leukocyte-endothelium interaction after liver transplantation in the rat

Flushing hepatic grafts immediately before revascularization with a specially designed rinse solution such as "Carolina rinse" has been reported to improve survival after liver transplantation in the rat. This study investigated the influence of Carolina rinse and adenosine rinse on early graft function, microcirculation, and leukocyte (WBC)-endothelial cell interaction of arterialized syngeneic orthotopic liver transplants in Lewis rats. Livers were preserved for 24 hr in University of Wisconsin solution and flushed immediately before reperfusion with either Ringer's lactate (group A: n = 7), Ringer's lactate + 0.2 mmol/liter adenosine (group B: n = 6), or Carolina rinse (group C: n = 7). Microvascular perfusion and WBC accumulation were assessed by intravital fluorescence microscopy. In group C, acinar perfusion was significantly improved, accompanied by a lower percentage of nonperfused sinusoids 1 hr after reperfusion (mean +/- SEM: 26 +/- 2% [group A], 21 +/- 2% [B], 11 +/- 1% [C], P < 0.01 for C vs. A or B). In addition, Carolina rinse and, to a lesser extent, adenosine rinse reduced the number of WBC sticking in sinusoids and postsinusoidal venules. Better graft function in group C was indicated by increased bile flow during the observation period of 90 min after reperfusion (0.5 +/- 0.3 ml/100 g liver [group A], 1.5 +/- 0.7 [B], 3.7 +/- 0.6 [C], P < 0.01 for C vs. A or B). We conclude that Carolina rinse is able to improve early excretory hepatocellular function, microvascular perfusion, and intrahepatic WBC accumulation after prolonged cold ischemia and reperfusion, but adenosine is unlikely to be the key component of this rinse solution.     

Use of the Medingen automated analyzer with evaluating unit as an automatic digital photometer]

Common errors in managing shock in children are failure to recognize shock, failure to recognize continuing blood loss, and inadequate replacement due to lack of familiarity with the normal blood volume of children. For practical purposes, the normal blood volume of every child is considered to be 40 ml/lb (88 ml/kg). In hypovolemic shock the blood volume is reduced by at least one fourth. For initial management, an intravenous line is established, blood is drawn for cross matching, and 10 ml/lb (22 ml/kg) of Ringer's lactate solution is administered as rapidly as possible. If this bolus, which represents one fourth of the normal blood volume, brings the blood pressure to normal, only maintenance fluid is then administered. If the child remains hypotensive, a second bolus of 10 ml/lb (22 ml/kg) is administered rapidly. Children who require a second bolus of Ringer's lactate solution nearly always need blood transfusion also. Many have occult bleeding, usually in the abdomen. If intra-abdominal bleeding is thought to be possible but not definitely present, paracentesis using an angiocath is performed. If no blood returns, 10 ml/lb (22 ml/kg) of saline is instilled and the return considered significant if more than slightly pink.     

Hypertonic saline dextran prime reduces increased intracranial pressure during cardiopulmonary bypass in pigs

Children and adults who develop neurologic deficits after cardiac surgery may experience cerebral ischemia during cardiopulmonary bypass. Increased intracranial pressure (ICP) may contribute to cerebral ischemia during bypass. Hypertonic saline dextran (HSD), a hyperosmotic, hyperoncotic resuscitation solution, decreases ICP in trauma resuscitation. We hypothesized that HSD would decrease ICP, reduce brain water, and reduce intravascular fluid requirements during bypass. Twelve swine were divided into two bypass groups: Group 1 (ISO = isotonic) received as prime 1 L of lactated Ringer's solution and 500 mL of 6% hydroxyethyl starch. Group 2 (HSD = hypertonic saline/dextran) received as prime 1 L of lactated Ringer's solution, 500 mL of 6% hydroxyethyl starch, and 1 mL/kg of 24% hypertonic saline/25% dextran. Normothermic bypass was instituted at 100 mL.kg-1.min-1. ICP increased significantly during bypass with ISO prime but not with HSD. Brain water in the cerebrum did not differ between groups but was reduced in the cerebellum to 75.9% +/- 1.4%. We conclude that HSD prevented any significant increase in ICP during normothermic bypass, and substantially improved fluid balance during bypass. In cardiac surgery patients in whom maintaining decreased ICP and reducing isotonic fluid administration is important, HSD may be a useful addition to the bypass prime solution.     

Prognostic value of blood lactate, base deficit, and oxygen-derived variables in an LD50 model of penetrating trauma

OBJECTIVE: To determine whether blood lactate, base deficit, or oxygen-derived hemodynamic variables correlate with morbidity and mortality rates in a clinically-relevant LD50 model of penetrating trauma. DESIGN: Prospective, controlled study. SETTING: University research laboratory. SUBJECTS: Anesthetized, mechanically-ventilated mongrel pigs (30+/-2 kg, n = 29). INTERVENTIONS: A captive bolt gun delivered a penetrating injury to the thigh, followed immediately by a 40% to 60% hemorrhage. After 1 hr, shed blood and supplemental crystalloid were administered for resuscitation. MEASUREMENTS AND MAIN RESULTS: After penetrating injury, 50.7+/-0.3% hemorrhage (range 50% to 52.5%), and a 1-hr shock period, seven of 14 animals died, compared with six of six animals after 55% to 60% hemorrhage, and 0 of nine animals after < or =47.5% hemorrhage. Only two of 13 deaths occurred during fluid resuscitation. At the LD50 hemorrhage, peak lactate concentration and base deficit were 11.2+/-0.8 mM and 9.3+/-1.5 mmol/L, respectively, and minimum mixed venous oxygen saturation, systemic oxygen delivery, and systemic oxygen consumption were 33+/-5%, 380+/-83 mL/min/kg, and 177+/-35 mL/min/kg, respectively. For comparison, baseline preinjury values were 1.6+/-0.1 mM, -6.7+/-0.6 mmol/L, 71+/-3%, 2189+/-198 mL/min/kg, and 628+/-102 mL/min/kg, respectively. Of all the variables, only lactate was significantly related to blood loss before and after fluid resuscitation in the 16 survivors. However, r2 values were relatively low (.20 to .50), which indicates that only a small fraction of the hyperiactacidemia was directly related to tissue hypoperfusion. In the whole population of survivors and nonsurvivors, both lactate and base deficit (but none of the oxygen-derived variables) correlated with blood loss. CONCLUSIONS: Arterial lactate is a stronger index of blood loss after penetrating trauma than base deficit or oxygen-derived hemodynamic variables. The reliability of arterial lactate depends on several factors, such as the time after injury, the proportion of survivors and nonsurvivors in the study population, and on factors other than tissue hypoxia.     

Plasma volume expansion with Haemaccel does not impair haemostasis during reduction mammaplasty

OBJECTIVES: An in vivo study under well-controlled conditions was undertaken to determine the effect of Haemaccel, a colloidal plasma volume expander, on normal haemostasis. METHODOLOGY: Twenty patients, who were admitted for reduction mammaplasty, were included in this study. A standardised anaesthesia protocol was followed with all patients. Ten patients received 500 ml Haemaccel and 10 controls received 1,500 ml Ringer's lactate, a crystalloid solution. The solutions were administered intravenously during surgery over a period of 30-40 minutes. Standardised clinical observations and haematological tests were done at the following time intervals: after anaesthesia but before infusion of the plasma substitute, immediately after infusion was completed, and 20, 40 and 60 minutes after infusion. RESULTS: The blood pressure, pulse rate and O2 saturation levels were not influenced by the treatment given. Haemodilution was similar for the two patient groups. The platelet count and plasma levels of fibrinogen decreased in parallel with haemodilution. Thereafter the platelet count gradually increased to pre-infusion counts at 60 minutes. The prothrombin time (PT), activated partial thromboplastin time (aPTT), thrombin time (TT) and platelet aggregation in response to adenosine diphosphate (ADP) and collagen were not affected by the plasma volume expander given. Arachidonic acid-induced aggregation decreased significantly after Ringer's lactate was given but did not change when Haemaccel was given. The bleeding time was prolonged slightly, but not significantly, from 7.4 +/- 1.6 minutes to 8.8 +/- 1.6 minutes with Ringer's lactate and from 6.9 +/- 2.0 to 9.7 +/- 3.7 minutes with Haemaccel. CONCLUSIONS: We could not find any scientific evidence that Haemaccel affects haemostasis; neither does it increase bleeding relative to Ringer's lactate.     

Effects of the stable prostacyclin analogue iloprost on mesenteric blood flow in porcine endotoxic shock

OBJECTIVE: To determine the effects of the stable prostacyclin analog, iloprost, in a porcine model of endotoxin-induced mesenteric ischemia. DESIGN: Prospective, experimental, randomized, controlled study. SETTING: Animal research laboratory at a university medical center. INTERVENTIONS: Pigs were randomized to receive a constant infusion of iloprost (0.18 microg/kg/min) or an equivalent amount of carrier solution (normal saline) 30 mins before being infused with endotoxin (100 microg/kg over 1 hr). The infusion with iloprost or carrier solution was continued for the duration of the experiment. MEASUREMENTS AND MAIN RESULTS: Twelve pigs (six per group), weighing between 20 and 22 kg, underwent laparotomy during which a magnetic flowprobe was placed around the superior mesenteric artery and an ileal tonometer was inserted. Thirty minutes before they were infused with endotoxin, the animals were randomized to receive intravenous iloprost or normal saline. Endotoxin was infused centrally over a 60-min period. Animals received normal saline at a rate of 1.2 mL/kg/min which was begun at the start of the endotoxin infusion. Data were measured at the end of the endotoxin infusion (E60) and 1 hr later (E120). Mean arterial pressure was not affected by the dosage of iloprost used in this experiment. After resuscitation, the cardiac output returned to baseline in the iloprost-treated group but remained decreased in the control group (2.6 +/- 0.5 vs. 1.6 +/- 0.4 L/min). Superior mesenteric blood flow increased 34% above baseline levels in animals pretreated with iloprost (from 363 +/- 85 to 485 +/- 81 mL/min). The superior mesenteric PCO2 was significantly higher (53 +/- 9 vs. 40 +/- 5 torr; 7.1 +/- 1.2 vs. 5.3 +/- 0.7 kPa) and the ileal intramucosal pH was significantly lower (7.07 +/- .28 vs. 7.44 +/- .23) in the control group than in the iloprost-treated group. CONCLUSIONS: Pretreatment with intravenous iloprost effectively increased intestinal blood flow in this model of endotoxin-induced mesenteric ischemia. This action of the drug resulted in an attenuation of ileal intracellular acidosis. Since low-dose iloprost had no effect on mean arterial pressure, it may be a useful adjunct in the treatment of sepsis and septic shock.     

Procalcitonin--a sepsis parameter in severe burn injuries

Procalcitonin (PCT) levels increase in patients with systemic infections; the highest levels have been found in sepsis. This study tested whether plasma procalcitonin level was related to sepsis, CRP, burn size, inhalation injury or mortality in severely burned patients over the entire clinical course. In 27 patients with 51 (20-91)% TBSA, PCT was measured three times weekly from admission over the entire course of stay in a single ICU. Daily scoring by the "Baltimore Sepsis Scale" was performed. The patients were assigned to three groups depending on the clinical course and outcome: A = no septic complications, B = septic complications-survivors, C = septic complications non-survivors. PCT levels were elevated slightly at admission (mean 2.1 ng/ml) except in three patients who suffered electrical burns (mean 15.7 ng/ml). PCT peak levels correlated well with the Scoring values (r = 0.84) while CRP did not (r = 0.64). Peak PCT levels were significantly higher (p < 0.005) in septic patients (B and C) who averaged 49.8+/-76.9 ng/ml, than in non-septic patients (A) who averaged peak levels of 2.3+/-3.7 ng/ml. The highest PCT levels were found immediately before death (86.8+/-97 ng/ml). Seven patients had an inhalation injury 3rd degree. In these patients at 24 h postburn, there was no relationship between PCT levels and inhalation injury but during the later days postburn there were significant differences in PCT levels in patients with versus without inhalation injury. All patients with inhalation injury 3rd degree developed septic complications. There was no positive correlation between the PCT-admission-levels and the TBSA, but there was a positive correlation between the TBSA and the mean peak PCT levels during the later days postburn (r = 0.73; p < 0.05). The cut-off value of 3 ng/ ml we found reliable to indicate severe bacterial or fungal infection. PCT values over 10 ng/ml increasing over the following days were found only in life-threatening situations due to systemic infections. The individual course of PCT in one patient is more important than absolute values. PCT presented in this study as a useful diagnostic parameter in severely burned patients.     

Dopexamine improves liver oxygenation during crystalloid resuscitation from experimental hemorrhagic shock

OBJECTIVE: To evaluate the effects of dopexamine administration on hemodynamic variables and tissue oxygen tensions during crystalloid resuscitation from hemorrhagic shock. DESIGN: Randomized, control trial. SETTING: An animal laboratory at a university center. SUBJECTS: Twelve piglets, mean weight 22 kg. INTERVENTIONS: The animals were anesthetized and bled to a state of hemorrhagic shock and resuscitated, using a crystalloid solution infused at a rate of approximately 2.6 mL/min/kg (total amount 208 mL/kg). Cardiac output and mean arterial pressure (MAP were measured as indicators of volume filling during the 20- to 30-min resuscitation period and during the follow-up period until 80 mins from the start of resuscitation. Dopexamine was administered by infusion at 6 micrograms/kg-min from the start of volume replacement (dopexamine group, n = 6). The rest of the animals (control group, n = 6) were given volume replacement only. MEASUREMENTS AND MAIN RESULTS: Systemic oxygen transport variables were calculated. Tissue oxygen tensions were continuously recorded from the liver, conjunctival layer, and via subcutaneous and transcutaneous electrodes in the abdominal region. MAP decreased from 119 +/- 2 (SEM) to 44 +/- 2 mm Hg and cardiac output decreased by 77% during the shock period. During resuscitation, cardiac output was restored in both groups. MAP increased close to the baseline during the early resuscitation period and decreased slowly during follow-up. Oxygen delivery remained at 46% of baseline, whereas systemic oxygen consumption was restored during resuscitation in both groups. Liver tissue oxygen tension increased well above baseline during resuscitation in the dopexamine group, and liver tissue oxygen tension was significantly higher than in the control group. After 60 mins of resuscitation, the liver oxygen tension decreased to control group values. None of the other tissue oxygen tensions showed any differences between groups. CONCLUSIONS: Dopexamine administration during crystalloid resuscitation from hemorrhagic shock was well tolerated and resulted in significant and specific, although transient, improvement in liver oxygenation.     

Spontaneous resolution of nonimmune hydrops in a fetus with a cystic adenomatoid malformation

BACKGROUND: Blood bank recommendations specify that Ringer's lactate solution (LR) should be avoided while transfusing blood. However, there are few studies either evaluating or quantifying increased coagulation during rapid infusion of LR and blood. DESIGN AND METHODS: Whole blood (WB, n = 25) and packed red blood cells (PRBC, n = 26) were rapidly admixed with normal saline (NS), Lactate solution and LR with 1 g (LR-1), 2 g (LR-2), and 5 g (LR-5) CaCl2/L solutions for assessment of infusion time, filter weight, and clot formation. RESULTS: No significant differences in infusion time or filter weight using WB or PRBC with NS or LR were seen. No significant difference in clot formation between NS and LR with WB or PRBC was found, but the presence of visible clot was increased in the LR-5 group (P = 0.013, WB, and P = 0.002, PRBC). CONCLUSION: A comparison of LR and NS with rapid infusion rates of blood showed no significant difference between infusion time, filter weight and clot formation. Blood bank guidelines should be revised to allow the use of LR in the rapid transfusion of PRBC.     

Hepatosplanchnic and peripheral tissue oxygenation during treatment of hemorrhagic shock: the effects of pentoxifylline administration

OBJECTIVE: To evaluate the effects of pentoxifylline (PF) administration on liver, gut, and peripheral oxygenation during crystalloid resuscitation of hemorrhagic shock. SUMMARY BACKGROUND DATA: Hypoperfusion of the hepatosplanchnic vascular bed and hypoxia of vital organs may be prolonged despite adequate therapy of hemorrhagic shock. Vasoconstriction, leukostasis, platelet aggregation, and red blood cell plugging could be the underlying causes. PF has been shown to counteract these effects, but its effects in a large animal shock model have been less studied. METHODS: Thirteen anesthetized piglets (mean weight 19.6 kg) were bled steadily to a mean arterial pressure (MAP) of 40 to 50 mmHg and a 70% reduction in cardiac output during 1 hour. These levels were maintained for an additional hour. The animals were resuscitated with acetated Ringer's solution according to MAP and cardiac output values and followed for 80 minutes (total 3 hours and 20 minutes). Seven piglets were given PF boluses (12.5 mg/kg) and infusion (0.2 mg/kg x min), and the rest (n = 6) served as controls. Hemodynamic and systemic oxygen transport variables were recorded. Liver parenchymal and peripheral tissue (subcutaneous, transcutaneous, conjunctival) oxygen tensions (PO2) were measured continuously with polarographic electrodes. Jejunal intramucosal pH (pHi) was calculated every hour by the luminal PCO2, obtained with a balloon tonometer, and arterial bicarbonate concentration. RESULTS: Cardiac output decreased by a mean of 76% during shock and was restored during resuscitation in both groups. MAP decreased from 110 to 40 mmHg but remained at 70 to 80 mmHg during resuscitation in both groups despite remarkable volume load (2.6 ml/min per kg). Liver parenchymal PO2 decreased from 29+/-1 to 15+/-1 mmHg during shock and increased to 36+/-2 mmHg in the PF group, whereas in control group it remained at 26 mmHg. The difference between groups was significant, but at the end of follow-up the liver PO2 decreased to 21 mmHg in both groups. Gut pHi, peripheral tissue oxygen tensions, and the plasma adrenaline and noradrenaline concentrations did not differ between the groups. CONCLUSIONS: Pentoxifylline improved specifically, although only transiently, liver tissue oxygenation. Perhaps the microvascular abnormalities after resuscitation of hemorrhagic shock are more prominent in the hepatic vascular bed, rendering PF specifically effective in that area. The lack of any effect of PF on gut and peripheral tissue oxygenation may have resulted from the persistent vasoconstriction and inadequate restoration of blood volume with crystalloid solution.     

Randomized long-term evaluation of bicarbonate-buffered CAPD solution

BACKGROUND: Over the past 15 years, lactate has been used successfully as a buffer in peritoneal dialysis solutions, although its effectiveness in the correction of uremic acidosis and its biocompatibility on peritoneal resident cells have been questioned. In addition, some investigators have suggested other potential adverse metabolic effects resulting from the unphysiologically high lactate flux into the body during CAPD. These potential problems associated with lactate-containing CAPD solution prompted the search for alternative buffer-containing solutions. Bicarbonate, the physiological buffer, was considered when the problem of calcium and magnesium carbonate solubility was solved by the use of a two-compartment bag system, allowing the mixing of bicarbonate and divalent cations immediately before infusion. The long-term tolerance, safety, efficacy and therapeutic value of a bicarbonate-buffered peritoneal dialysis solution were evaluated in this study. METHODS: This open, randomized, controlled, multicenter study comparing a 34 mmol/liter bicarbonate- with a 35 mmol/liter lactate-buffered peritoneal dialysis solution was performed in two consecutive 12-week-treatment phases. Fourteen Centers participated in this trial. RESULTS: A total of 69 out of initially 123 randomized patients completed the six-month study period (36 patients in the bicarbonate group and 33 in the lactate group). While the arterial acid base status of the total study population did not change during the study period and no significant difference was observed between the two treatment groups, the acid-base status of patients in the bicarbonate group entering the study with a metabolic acidosis significantly improved (mean +/- SD; blood pH: baseline = 7.361 +/- 0.05, week 12 = 7.380 +/- 0.04, P < 0.05; week 24 = 7.388 +/- 0.03 P < 0.05; plasma bicarbonate: baseline = 19.49 +/- 3.01 mmol/liter, week 12 = 21.16 +/- 2.63 mmol/liter, P < 0.01; week 24 = 21.51 +/- 2.42 mmol/liter, P < 0.01). No significant changes were recorded in acidotic patients treated with the conventional lactate-buffered solution. The changes in plasma bicarbonate from baseline during the study was significantly different between the groups (week 12: lactate = +0.11 +/- 2.21 mmol/liter, bicarbonate = +1.69 +/- 2.55 mmol/liter, P < 0.05, 95% confidence interval for the difference 0.21 to 2.94 mmol/liter; week 24: lactate = +0.03 +/- 2.48 mmol/liter, bicarbonate = +1.82 +/- 2. 96 mmol/liter, P < 0.05, 95% confidence interval for the difference 0.16 to 3.42 mmol/liter). The normalized protein catabolic rate (nPCR) slightly but significantly decreased in the lactate group (baseline -0.90 +/- 0.23 g/kg/day, week 24 -0.83 +/- 0.21 g/kg/day, P < 0.01) and increased in the bicarbonate group (baseline +0.89 +/- 0.28 g/kg/day, week 24 +0.92 +/- 0.26 g/kg/day, P < 0.05). Changes from baseline between groups were significant (week 24, lactate = -0. 099 +/- 0.15 g/kg/day, bicarbonate = 0.049 +/- 0.12 g/kg/day, P < 0. 01, 95% confidence interval for the difference 0.068 to 0.229 g/kg/day). Other evaluated parameters (biochemical profile, peritoneal function parameters, dialysate protein loss) did not differ significantly between the two groups. No adverse effects related to the study solution were recorded. CONCLUSIONS: These results support the efficacy and safety of bicarbonate-buffered peritoneal solutions in a controlled randomized comparison for up to six months. Peritoneal dialysis solutions containing the physiological buffer bicarbonate might effectively replace conventional lactate-buffered CAPD solutions.