The effects of ketamine and propofol on bacterial translocation in rats after burn injury

BACKGROUND: Bacterial translocation (BT) occurs after thermal injury and may result from an ischemic intestinal insult. The aim of the study was to investigate the effects of ketamine and propofol as anesthetic agents on BT in an animal model of burn injury. METHODS: Sixty male Wistar Albino rats were randomly assigned to six groups of 10 rats each. Anesthesia was induced and maintained with ketamine in groups 1, 2 and 3 and with propofol in groups 4, 5 and 6 during 6 h. Groups 2, 3, 5 and 6 received 30% total body surface area (TBSA) third-degree burns. Groups 1 and 4 had no burn injury. Then, they were allowed to recover from the anesthesia at the end of 6 h. Mean arterial pressure (MAP) was monitored continuously and maintained within 10% of baseline (before burn injury) levels in all animals. Animals in groups 3 and 6 had a laparotomy to obtain a tissue sample from the terminal ileum for determination of intestinal lipid peroxidation by-product malondialdehyde (MDA) before (baseline) and 6 and 24 h after burn injury (ABI). So these animals were not included in the BT studies. At postburn 24 h, animals in groups 1, 2 and 4, 5 were sacrified and samples were taken from the mesenteric lymph nodes (MLN), liver and spleen for bacteriologic cultures. RESULTS: The incidence of BT was found to be significantly higher in group 2 than in all the other groups. Bacterial translocation incidence of group 5 was not significantly different from that of groups 4 and 1. Group 5 was associated with a significantly reduced number of enteric organisms per gram of tissue compared to group 2. Baseline MDA contents of groups 3 and 6 were similar. Ileal MDA levels were increased in group 3, but there were no significant changes in group 6 at 6 and 24 h ABI compared to baseline. CONCLUSION: Our results suggest that propofol as an anesthetic agent may prevent BT by scavenging reactive oxygen species and inhibiting lipid peroxidation in an animal model of burn injury.     

严重烧伤早期肠道营养对肠道脂肪吸收的影响

将健康雄性贵州小型香猪12只,致体表面积Ⅲ度30％烧伤后,分为早期及延迟喂养两组。分别于伤前及伤后4、7及10天进行门静脉血流量测定及吸收功能测定。结果表明,烧伤后肠道吸收功能随门静脉血流量而变化,而肠道本身的吸收功能并没有大幅度减少。早期肠道营养能明显增加脂肪的吸收量。结果提示,如果能及时而有效地改善门静脉系血循环状况,肠道吸收功能可明显改善,而早期肠道营养则是达到此目的的一个有效手段。     

严重烧伤早期肠道营养对肠道脂肪吸收的影响

将健康雄性贵州小型香猪１２只，致体表面积Ⅲ度３０％烧伤后，分为早期及延迟喂养两组。分别于伤前及伤后４、７及１０天进行门静脉血流量测定及吸收功能测定。结果表明，烧伤后肠道吸收功能随门静脉血流量而变化，而肠道本身的吸收功能并没有大幅度减少。早期肠道营养能明显增加脂肪的吸收量。结果提示，如果能及时而有效地改善门静脉系血循环状况，肠道吸收功能可明显改善，而早期肠道营养则是达到此目的的一个有效手段。     

Effects of anesthesia, surgery, fluid resuscitation, and endotoxin administration on postburn bacterial translocation

The aim of the study reported here was to assess the effects of some clinically relevant factors on the incidence and outcome of postburn bacterial translocation. Miniature pigs in 8 groups (n = 6 in each) underwent: (1) general anesthesia (GA); (2) operation (insertion of Swan-Ganz, arterial, and portal catheters) under GA; (3) burn (40% total body surface area, third degree, under GA); (4) burn and operation; (5) burn, operation, and resuscitation (Parkland); (6) burn, operation, and resuscitation plus endotoxin (100 micrograms/kg IV bolus, 2nd day). Groups 1-6 were killed at 48 hours and tissue samples were harvested for bacteriologic culture. Groups 7 and 8 were the same as 2 and 5, respectively, but were killed at 96 hours. Resuscitation and endotoxin increased postburn bacterial translocation but only endotoxin promoted systemic sepsis. In the absence of additional trauma, translocated bacteria were cleared by 96 hours postburn.     

Ventilatory patterns following burn injury and effect of sulfamylon.

Seven burn patients treated with silver nitrate dressings were studied during the first 10 days after injury. Minute ventilation, oxygen consumption, and ventilatory equivalent were measured. Minute ventilation was increased two- to threefold, as was oxygen consumption. Ventilatory equivalent was only slightly increased. THree patients were initially treated with silver nitrate, and then, when clinically stable, were switched to Sulfamylon. They showed a 50% rise in ventilation, tidal volume, ventilatory equivalent, and a slight increase in respiratory rate and VD/VT. In addition, their PO2 increased and base excess fell. Five normal subjects were then given Diamox, and their minute ventilation, O2 consumption, and ventilatory equivalent were measured at rest, with a standard exercise, and with an added dead space. Diamox produced only a 25% increase in minute ventilation and ventilatory equivalent. The results suggest that, although some of the increased ventilation of Sulfamylon is due to carbonic anhydrase inhibition, another factor, such as pain casued by the topical agent, also plays a role.     

Lung water changes after thermal injury. The effects of crystalloid resuscitation and sepsis.

Respiratory failure after thermal injury is common, but the etiologic roles of high volume crystalloid resuscitation, hypoproteinemia, inhalation injury, or sepsis have not been specifically defined in human studies. We used the thermal-green dye double indicator dilution measurement of extravascular lung water (EVLW) to follow daily lung water changes in seven severly burned adult patients, resuscitated with only crystalloid solutions. An average weight gain of 21.3 kg, a 30% increase (p < 0.001), was present two to three days after admission. Admission EVLW for all patients was 7.9 +/- 1.2 ml/kg, (means +/- SD), and EVLW at the time of maximal weight gain was 5.9 +/- 1.4 ml/kg, a 25% decrease (p < 0.05). Admission pulmonary artery wedge pressure (PAWP) was 8 +/- 3 mmHG, which was not significantly different from PAWP of 13 +/- 4 mmHg at the time of maximal weight gain. In the three patients who died of sepsis, their terminal weight averaged 17.8 kg (27%) above their admitting weight (p < 0.01) and EVLW was 26.4 +/- 4.4 ml/kg, a 200% increase (p < 0.02) from admission. Their terminal PAWP averaged 22 +/- 2 mmHg, a 170% increase (p < 0.005). None of these patients had an increase in EVLW until clinical signs of sepsis occurred and the rise in EVLW preceded the rise in PAWP. Calculated mean plasma colloid osmotic pressure (PCOP) on admission was 20.7 +/- 4.9 mmHg; at the time of maximal weight gain, it was 8.6 +/- 1.7 mmHg (p < 0.001). The PCOP-PAWP gradient fell to -4 +/- 4 mmHg (p < 0.001) at the time of maximal weight gain and remained less than +4 mmHg throughout the study period in all patients. We conclude that massive crystalloid resuscitation while maintaining PAWP below 15 mmHg does not cause an increase in EVLW during the first four days after thermal injury. EVLW actually decreases slightly in all patients despite marked weight gain, hypoproteinemia and a negative PCOP-PAWP gradient. EVLW does not correlate with the PCOP-PAWP gradient in either septic or nonseptic periods. Three patients had severe inhalational injury and normal EVLW for the first four postburn days. It therefore appears that significant interstitial edema does not result from inhalational injury. There is also no evidence that thermal injury causes an early increase in pulmonary capillary permeability. The occurrence of sepsis, however, results in rapid accumulation of lung water, without any change in hydrostatic or osmotic forces. This study supports the primary role of sepsis in altering pulmonary capillary permeability with resulting pulmonary edema.     

The effect of hypertonic saline resuscitation on bacterial translocation after hemorrhagic shock in rats

Translocation of enteric bacteria occurs in rats after hemorrhagic shock. A proposed mechanism involves intestinal mucosal injury by hypoperfusion. Recent work suggests that moderate hypovolemia causes gut arteriolar constriction, which is ameliorated by hypertonic saline resuscitation. Bacterial translocation should, therefore, be reduced when hypertonic saline (HS) is used as the resuscitative fluid. Seventy-eight Sprague-Dawley rats were anesthetized and subjected to 30 minutes of hemorrhagic shock (systolic blood pressure 30 to 50 mm Hg) through a modified Wigger's model. Resuscitation was performed with either shed blood (B), 3% HS + 1/2B (1:1), or with 7.5% HS + 1/2B (1:1). Spleen, liver, and mesenteric lymph nodes were sent for quantitative culture 24 hours later. Translocation occurred if enteric organisms were cultured from at least one organ. Statistical analysis used the Fisher exact test. Compared to autotransfusion, hemodilutional resuscitation from hemorrhagic shock with hypertonic saline resulted in a significant reduction in bacterial translocation (p values were 0.03 and 0.04 for 3% and 7.5% hypertonic saline, respectively). The reduction in translocation after hypertonic saline resuscitation may be the consequence of microcirculatory alterations preventing gut hypoperfusion.     

Randomized trial of efficacy of crystalloid and colloid resuscitation on hemodynamic response and lung water following thermal injury

To assess the effects of crystalloid and colloid resuscitation on hemodynamic response and on lung water following thermal injury, 79 patients were assigned randomly to receive lactated Ringer's solution or 2.5% albumin-lactated Ringer's solution. Crystalloid-treated patients required more fluid for successful resuscitation than did those receiving colloid solutions (3.81 vs. 2.98 ml/kg body weight/% body surface burn, p less than 0.01). In study phase 1 (29 patients), cardiac index and myocardial contractility (ejection fraction and mean rate of internal fiber shortening, Vcf) were determined by echocardiography during the first 48 hours postburn. Cardiac index was lower in the 12- to 24-hour postburn interval in the crystalloid group, but this difference between treatment groups had disappeared by 48 hours postburn. Ejection fractions were normal throughout the entire study, while Vcf was supranormal (p less than 0.01 vs. normals) and equal in the two resuscitation groups. In study phase 2 (50 patients), extravascular lung water and cardiac index were measured by a standard rebreathing technique at least daily for the first postburn week. Lung water remained unchanged in the crystalloid-treated patients (p greater than 0.10), but progressively increased in the colloid-treated patients over the seven day study (p less than 0.0001). The measured lung water in each treatment group was significantly different from one another (p less than 0.001). Cardiac index increased progressively and identically in both treatment groups over the study period (p less than 0.01). These data refute the existence of myocardial depression during postburn resuscitation and document hypercontractile left ventricular performance. The addition of colloid to crystalloid resuscitation fluids produces no long lasting benefit on total body blood flow, and promotes accumulation of lung water when edema fluid is being reabsorbed from the burn wound.     

The effect of indomethacin on the cytokine cascade and body temperature following burn injury in rats.

This study investigates the hypothesis that indomethacin's ability to prevent "fever" following burn injury in rats is mediated via decreased plasma concentrations of IL-6, the putative mediator of increased body temperature. Sprague-Dawley rats had radio transmitters and osmotic pumps containing indomethacin placed in the peritoneal cavity. Seven days later full thickness scald burns to 50% of the body surface area were produced. Following burn injuries, daily blood samples were obtained from a carotid catheter for assay of lipopolysaccharide (LPS), interleukin-1alpha (IL-1alpha), IL-1beta, tumor necrosis factor-alpha (TNF-alpha) and IL-6. In addition, body temperature (T(B)) and activity index were obtained every five minutes by telemetry. There were four experimental groups: burn + indomethacin (B-In); burn + polyethylene glycol (Peg) (B-Peg); control + indomethacin (C-In); and control + Peg (C-Peg). Burned animals demonstrated a significant two-fold increase in plasma IL-1alpha levels (p=0.004) and a seven-fold increment in IL-6 (p=0.0001) through the 7th PBD, and indomethacin administration had no significant effect upon the cytokine plasma levels. There were no significant increases in IL-1beta, TNF-alpha or LPS in any group. Indomethacin eliminated the chronic increase in T(B) following burn injury, and this effect was not produced by changes in plasma levels of the endogenous pyrogens IL-1alpha and IL-6.     

The effect of resuscitation on inhalation injury

Eighteen chronically instrumented sheep with lung-lymph catheters were studied. Inhalation injury was produced in 12 animals under halothane anesthesia and then studied for 24 hours. Six of the animals received 70 ml/m2/hr body surface area of 5% dextrose in Ringer's lactated solution (normal maintenance fluid requirements for sheep), and six received 140 ml/m2/hr (twice normal maintenance fluid requirements for sheep). Six additional animals were anesthetized, insufflated with air instead of smoke, and received 70 ml/m2/hr of resuscitation fluid (sham group). Twelve hours after injury, the recorded variables from the animals that were smoked and had received a high fluid resuscitation were not different from the sham group whereas the group with low-volume fluid resuscitation had a much higher lung-lymph flow and lymph-to-plasma protein concentration ratio and a lower cardiac output. The lung microvascular permeability changes seen with smoke inhalation are made worse by inadequate fluid resuscitation.     

The effect of N-acetylcysteine on oxidative stress in intestine and bacterial translocation after thermal injury

Ischemia due to transient splanchnic vasoconstriction following major burns causes oxidative and/or nitrosative damage in intestinal tissue followed by reperfusion injury. Thus, burn injury leads to breakdown in the intestinal mucosal barrier which can induce bacterial translocation (BT). As an antioxidant and anti-inflammatory agent the protective effects of N-acetylcysteine (NAC) are documented in several studies. This study was designed to determine the effect of NAC treatment on the oxidative stress in the intestine and BT after burn injury. To evaluate this, 32 Wistar rats were randomly divided into four groups as sham (n = 8), burn (n = 8), pre-burn, NAC injection (150 mg kg⁻¹, intraperitoneally) 15 min before thermal injury (n = 8), post-burn, NAC injection (150 mg kg⁻¹, intraperitoneally) 2 h after thermal injury. Under anesthesia, the shaved dorsal skin of rats was exposed to boiling water for 12 s to induce burn injury in a standardized manner. Twenty-four hours later, tissue samples from mesenteric lymph nodes (MLN), spleen, and liver were obtained under sterile conditions for microbiological analysis and ileum samples were harvested for biochemical analysis. In the burn group, the incidence of isolating bacteria in MLN, spleen, and liver specimens was significantly higher than other groups. NAC treatment prevented burn-induced BT in both pre- and post-burn groups. Thermal injury caused a significant decrease in glutathione (GSH) level, significant increases in malondialdehyde (MDA) and myeloperoxidase (MPO) activity at post-burn 24th hour. Treatment of rats with NAC significantly elevated the reduced GSH levels while decreasing MDA levels and MPO activity. These data suggested that NAC has a crucial cytoprotective role in intestinal mucosal barrier and preventive effects against burn injury-induced BT.     

The effects of burn injury and fluid resuscitation on cardiac function in vitro

The effects of a 30% full-thickness total body surface area scald burn on in vitro mechanical cardiac function was studied in Sprague-Dawley rats. The findings were a 50% decrease in tension development and velocities of contraction and relaxation, when papillary muscle functions from sham and unresuscitated burned animals were compared. Fluid resuscitation synchronous with burning completely reversed the defects in papillary muscle function. This defect in function was partially transferable to normal muscles incubated in serum from burned rats.     

The degree of bacterial translocation is a determinant factor for mortality after burn injury and is improved by prostaglandin analogs.

Bacterial translocation and related mortality rates were examined in previously transfused BALB/c mice that were gavaged with 14C radioisotope-labeled Escherichia coli before inflicting a 20% full-thickness flame burn. Radionuclide counts were measured in blood obtained by retro-orbital puncture 4 hours postburn, and survival was recorded for 10 days. Radionuclide counts in the blood correlated well with both radionuclide counts and numbers of viable bacterial in the tissues. Survivors had significantly less bacterial translocation as evidenced by blood radionuclide counts compared with nonsurvivors, and there was a significant inverse correlation between the degree of translocation and the length of survival. In the next experiment, the prostaglandin E (PGE) analogs misoprostol, enisoprost, or 16,16-dimethyl PGE2 were administered to transfused animals for 3 days before burn. Prostaglandin E analogs significantly reduced bacterial translocation as measured by blood radionuclide counts 4 hours postburn and improved survival. The data demonstrate that the intensity of bacterial translocation after burn injury is significantly associated with subsequent death. Improvement of survival by PGE analogs is associated with decreased bacterial translocation.     

The effect of ethyl pyruvate on oxidative stress in intestine and bacterial translocation after thermal injury

BACKGROUND: Thermal injury causes a breakdown in the intestinal mucosal barrier due to ischemia reperfusion injury, which can induce bacterial translocation (BT), sepsis, and multiple organ failure in burn patients. The aim of this study was to investigate the effect of ethyl pyruvate (EP) on intestinal oxidant damage and BT in burn injury. MATERIALS AND METHODS: Thirty-two rats were randomly divided into four groups. The sham group was exposed to 21 degrees C water and injected intraperitoneal with saline (1 mL/100 g). The sham + EP group received EP (40 mg/kg) intraperitoneally 6 h after the sham procedure. The burn group was exposed to thermal injury and given intraperitoneal saline injection (1 mL/100 g). The burn + EP group received EP (40 mg/kg) intraperitoneally 6 h after thermal injury. Twenty-four hours later, tissue samples were obtained from mesenteric lymph nodes, spleen, and liver for microbiological analysis and ileum samples were harvested for biochemical analysis. RESULTS: Thermal injury caused severe BT in burn group. EP supplementation decreased BT in mesenteric lymph nodes and spleen in the burn + EP group compared with the burn group (P < 0.05). Also, burn caused BT in liver, but this finding was not statistically significant among all groups. Thermal injury caused a statistically significant increase in malondialdehyde and myeloperoxidase levels, and EP prevented this effects in the burn + EP group compared with the burn group (P < 0.05). CONCLUSION: Our data suggested that EP can inhibit the BT and myeloperoxidase and malondialdehyde production in intestine following thermal injury, suggesting anti-inflammatory and anti-oxidant properties of EP.     

The effect of dexamethasone and endotoxin administration on biliary IgA and bacterial adherence.

Adherence of bacteria to the intestinal epithelial cell may be the crucial initiating event for invasion and translocation and is normally prevented by both immune (IgA) and nonimmune (mucus, peristalsis, desquamation) mucosal defense mechanisms. The purpose of the present study was to examine the effect of endotoxin administration on mucosal immunity and to define the role of glucocorticoids, commonly released during endotoxicosis, in this process. Thirty female Fisher rats were randomly assigned to three groups of 10 animals each. Group I (CONT), was fed rat chow and H2O ad lib., Group II (DEX) was administered 0.8 mg/kg subcutaneously of dexamethasone, and Group III (ETX) was given 1 mg/kg of endotoxin. Twenty-four hours later animals were sacrificed and mesenteric lymph nodes and vigorously washed stool-free ceca were collected and cultured. Bile was collected and assayed for IgA from 5 animals in each group. A significant decrease (P < 0.05) in secretory IgA was noted in animals treated with either dexamethasone or endotoxin (CONT = 332 +/- 42, DEX = 78 +/- 24, ETX = 68 +/- 16 micrograms/mg protein +/- SEM). No difference in S-IgA between animals in the dexamethasone-treated group and the endotoxin-treated group was noted (P = NS). A statistically significant increase (P < 0.001) in bacteria adherent to the cecal wall in both the dexamethasone-treated rats and the endotoxin-treated rats over that in = 7.5 +/- 0.8, CONT = 6.4 +/- 0.6 cfu/g(log10) +/- SD). Our results suggest that endotoxin or glucocorticoid administration results in significant bacterial adherence to the cecal mucosa and a decrease in IgA.(ABSTRACT TRUNCATED AT 250 WORDS)     

Negative inotropic effect of albumin resuscitation for shock.

The inotropic effects of albumin were studied in 94 seriously injured patients who received an average of 14.5 transfusions, 9.2 liters of crystalloid and 0.9 liters of plasma prior to end of operation; 46 patients, by random selection, received added albumin averaging 31 gm during operation, 198 gm during the early postoperative period of extravascular fluid sequestration, and 395 gm during the first 4 days of the later fluid mobilization period. Left ventricular stroke work index (LVSWI) was plotted against pulmonary wedge pressure (Ppw) in 22 patients who had indwelling thermistor pulmonary artery catheters at the time of the first study. Calculated heart work units (WU) were derived from the pulse pressure, mean arterial pressure, pulse rate, and central venous pressure (CVP) in patients without LVSWI measurements. Albumin supplementation increased serum albumin (4.2 vs. 2.9 gm%), plasma volume, CVP (15 vs. 9 cm H2O), but did not alter red cell volume (1,531 vs. 1,519 ml). The ratio of LVSWI/Ppw fell in albumin patients (1.9 +/- 1.6 vs. 4.8 +/- 1.8), and the ratio of WU/CVP was significantly depressed in albumin patients (4.9 +/- 2.3 vs. 7.3 +/- 2.1). The slopes of the LVSWI/Ppw and WU/CVP were shifted to the right in albumin patients. This negative inotropic effect was associated with impaired oxygenation, as reflected by an increased ratio of inspired oxygen per arterial oxygen tension (0.62 +/- 0.06 vs. 0.33 +/- 0.1). Finally, 24 of the 46 albumin-treated patients were digitalized for heart failure, compared to only 11 of the 48 nonalbumin patients. Pending subsequent studies, albumin should be considered a potentially negative inotropic agent.     

清胰汤对急性出血坏死性胰腺炎肠道细菌及内毒素移位的影响

目的探讨清胰汤对急性出血坏死性胰腺炎(AHNP)大鼠肠道细菌、内毒素移位的影响。方法SD大鼠随机分成AHNP组,AHNP+清胰汤治疗(QYT)组,假手术(SO)组。AHNP组与QYT组大鼠建立AHNP模型,SO组大鼠仅开腹翻动胰腺。QYT组造模后进行清胰汤胃灌注,另两组生理盐水灌胃,24 h后检测门静脉血内毒素(ET)浓度和大肠杆菌DNA含量(Ct值)。结果QYT组ET浓度、大肠杆菌DNA含量均低于AHNP组。结论清胰汤可降低实验性AHNP大鼠门静脉血中细菌DNA表达和内毒素浓度,减少肠道的细菌、内毒素移位。