Fluid Resuscitation Regimens Research Articles

Bioelectrical impedance analysis-guided fluid management promotes primary fascial closure after open abdomen: a randomized controlled trial

BackgroundFluid overload (FO) after resuscitation is frequent and contributes to adverse outcomes among postinjury open abdomen (OA) patients. Bioelectrical impedance analysis (BIA) is a promising tool for monitoring fluid status and FO. Therefore, we sought to investigate the efficacy of BIA-directed fluid resuscitation among OA patients.MethodsA pragmatic, prospective, randomized, observer-blind, single-center trial was performed for all trauma patients requiring OA between January 2013 and December 2017 to a national referral center. A total of 140 postinjury OA patients were randomly assigned in a 1:1 ratio to receive either a BIA-directed fluid resuscitation (BIA) protocol that included fluid administration with monitoring of hemodynamic parameters and different degrees of interventions to achieve a negative fluid balance targeting the hydration level (HL) measured by BIA or a traditional fluid resuscitation (TRD) in which clinicians determined the fluid resuscitation regimen according to traditional parameters during 30 days of ICU management. The primary outcome was the 30-day primary fascial closure (PFC) rate. The secondary outcomes included the time to PFC, postoperative 7-day cumulative fluid balance (CFB) and adverse events within 30 days after OA. The Kaplan–Meier method and the log-rank test were utilized for PFC after OA. A generalized linear regression model for the time to PFC and CFB was built.ResultsA total of 134 patients completed the trial (BIA, n = 66; TRD, n = 68). The BIA patients were significantly more likely to achieve PFC than the TRD patients (83.33% vs. 55.88%, P < 0.001). In the BIA group, the time to PFC occurred earlier than that of the TRD group by an average of 3.66 days (P < 0.001). Additionally, the BIA group showed a lower postoperative 7-day CFB by an average of 6632.80 ml (P < 0.001) and fewer complications.ConclusionAmong postinjury OA patients in the ICU, the use of BIA-guided fluid resuscitation resulted in a higher PFC rate and fewer severe complications than the traditional fluid resuscitation strategy.

2964 Real World Evidence Demonstrates a Difference in the Presenting Characteristics of Cirrhotic Patients Who Received Albumin Compared to Those Who Received Only Crystalloids

INTRODUCTION: Cirrhosis affects over 633,000 adults in the US with recent mortality rates increasing by 3.4% annually. Readmission rates have also been shown to be high. These patients may be resuscitated with albumin, crystalloids, or both. METHODS: This study used real-world data to examine differences in the burden of disease among adults admitted with cirrhosis who were treated with albumin (&lt;24 hours (early) versus &gt;24 hours (late) after admission) versus crystalloids alone, between January 1, 2009, and December 31, 2016. We used a nationwide Electronic Health Record database (Cerner Health Facts®) and compared Model for End-stage Liver Disease Sodium (MELD-Na) score and Elixhauser Comorbidity Index across the fluid resuscitation groups. RESULTS: We identified 86,432 patients admitted with cirrhosis. The mean age was 59.2 years and the majority (55.4%) were male. Patients who received albumin (n = 26,835) had higher MELD-Na scores at presentation (mean score 22.0 in patients treated early and mean score 19.5 in patients treated late), versus patients who received only crystalloids (n = 59,597; mean score 14.1). Additionally, at presentation, patients who received albumin had a higher Elixhauser Comorbidity Index (mean 18.8 and 19.9 in patients receiving albumin early versus late respectively) versus patients who received crystalloids alone (mean 16.3). CONCLUSION: Cirrhotic patients who were treated with albumin had, at presentation, a higher MELD-Na score and Elixhauser Index, which represents a greater burden of disease compared to patients treated with only crystalloids. Further research is needed to examine differences in clinical and economic outcomes, including complications of cirrhosis such as acute kidney injury, spontaneous bacterial peritonitis, ascites, and procedures of large volume paracentesis, following different fluid resuscitation regimens.

Restricted fluid resuscitation in suspected sepsis associated hypotension (REFRESH): a pilot randomised controlled trial.

To determine if a regimen of restricted fluids and early vasopressor compared to usual care is feasible for initial resuscitation of hypotension due to suspected sepsis. A prospective, randomised, open-label, clinical trial of a restricted fluid resuscitation regimen in the first 6h among patients in the emergency department (ED) with suspected sepsis and a systolic blood pressure under 100mmHg, after minimum 1000ml of IV fluid. Primary outcome was total fluid administered within 6h post randomisation. There were 99 participants (50 restricted volume and 49 usual care) in the intention-to-treat analysis. Median volume from presentation to 6h in the restricted volume group was 2387ml [first to third quartile (Q1-Q3) 1750-2750ml]; 30ml/kg (Q1-Q3 32-39ml/kg) vs. 3000ml (Q1-Q3 2250-3900ml); 43ml/kg (Q1-Q3 35-50ml/kg) in the usual care group (p < 0.001). Median duration of vasopressor support was 21h (Q1-Q3 9-42h) vs. 33h (Q1-Q3 15-50h), (p = 0.13) in the restricted volume and usual care groups, respectively. At 90-days, 4 of 48 (8%) in the restricted volume group and 3 of 47 (6%) in the usual care group had died. Protocol deviations occurred in 6/50 (12%) in restricted group and 11/49 (22%) in the usual care group, and serious adverse events in fourcases (8%) in each group. A regimen of restricted fluids and early vasopressor in ED patients with suspected sepsis and hypotension appears feasible. Illness severity was moderate and mortality rates low. A future trial is necessary with recruitment of high-risk patients to determine effects on clinical outcomes in this setting.

The problem of burns

Background: Burns due to accidents are a common cause of morbidity and mortality in the Indian sub-continent. The causes being preventive, warrant a better understanding of the epidemiology to know the seriousness of the situation, implement better medical care and prevent such accidents. Aim was to study the morbidity and mortality related to percentage of burns.Methods: This is a retrospective observational study where patients admitted with burns 2013 and 2015 were evaluated. Data with respect to sex, age, percentage of burns, air-way burns, mode and cause of burns, cause of death and length of hospitalization were analyzed.Results: 65.3% of the patients were females and 34.7% males, with a male: female ratio of 0.53:1. A total mortality of 43.71% was seen. Maximum patients belonged to age group 21-40 years which also constituted 28.74% (highest) of the above total mortality. More than 50 % mortality was seen in patients with more than 41% burns. Air way burns were present in 41.31% of the cases; of which 85.51% of cases did not survive. Death due to hypovolemic shock (42.47%) was the main cause of death in the initial 4 days of admission; whereas septicemic shock (57.53%) from the 5th day onward.Conclusions: Morbidity and mortality due to burns is still very high in India, especially in young adults of age groups 21- 40 years. A higher case load for females as seen, being nearly double in in relation to males. Better fluid resuscitation regimens with adequate control of infection is the need of the hour to bring down the mortality. Female sex and more than 41% burns predicts higher mortality. Involvement of the respiratory tract, also predicts higher mortality and may be taken as a reliable indicator of the severity of burns. In the present scenario, we should stress more over the prevention of burns, to easily make available affordable and cheap medical care for the patients and to minimize post burn disability as much as possible.

Effects of resuscitation by different formulation on oxygen metabolism during shock stage of burn injury in swine

To explore the effects of different fluid resuscitation regimens on oxygen metabolism during shock stage of burn injury in swine. Twelve Bama miniature swines were divided into crystal and colloid group (Group 1) and Parkland group (Group 2) according to the random number table. The swine models of burns shock were established. The fluid resuscitation was begun at post injury hour (PIH) 2 according to Chinese formulation or Parkland's formulation, respectively. The blood pressure, urine volume, heart rate, central venous pressure (CVP), pulmonary capillary wedge pressure (PCWP) were recorded. The liquid volume was calculated at the first and second PIH 24. The changes in oxygen delivery (DO2), oxygen consumption (VO2), oxygen extraction (O2Ext) and D-lactate (D-LA) were determined before injury and at PIH 4, 8, 24, and 48. Statistical analyses were performed. There were no statistical differences between the two groups in blood pressure, urine volume, heart rate, CVP, PCWP in every interval (all P>0.05). The resuscitation liquid volume in the two groups during the first and second PIH 24 conformed to the domestic consensus. The VO2 at PIH 8 was significantly higher than that of pre-burn in both groups [(190±29) vs (83±42) L·min(-1)·m(-2,) (149±33) vs (85±15) L·min(-1)·m(-2,) both P<0.05], and the VO2 at PIH 8 was significantly higher in Group 1 than that in Group 2 (P<0.05). The DO2 at PIH 24 in Group 1 was significantly lower than that in Group 2 [(686±72) vs (853±81) L·min(-1)·m(-2,) P<0.05]. There were no significant differences between the two groups in O2Ext at any time points (all P>0.05). The D-LA at PIH 8 was significantly higher in Group 1 than that in Group 2 [(53±4) vs (45±6) mmol/L, P<0.05]. There are no significant differences in the resuscitation effects of the crystal and colloid resuscitation regimen and Parkland's formulation on oxygen metabolism during shock stage of burn injury in swine.

Blood Flow Versus Hematocrit in Optimization of Oxygen Transfer to Tissue During Fluid Resuscitation

The effectiveness of fluid resuscitation regimens in hemorrhagic trauma is assessed based on its ability to increase oxygen concentration in tissue. Fluid resuscitation using both crystalloids and colloids fluids, creates a dilemma due to its opposing effects on oxygen transfer. It increases blood flow thereby augmenting oxygen transport but it also dilutes the blood simultaneously and reduces oxygen concentration thereby reducing oxygen transport. In this work we have studied these two opposing effects of fluid therapy on oxygen delivery to tissue. A mathematical model of oxygen diffusion from capillaries to tissue and its distribution in tissue was developed and integrated into a previously developed hemodynamic model. The capillary-tissue model was based on the Krogh structure. Compared to other models, fewer simplifying assumptions were made leading to different boundary conditions and less constraints, especially regarding capillary oxygen content at its venous end. Results showed that oxygen content in blood is the dominant factor in oxygen transport to tissue and its effect is greater than the effect of flow. The integration of the capillary/tissue model with the hemodynamic model that links administered fluids with flow and blood dilution indicated that fluid resuscitation may reduce oxygen transport to tissue.

Effects on vascular permeability with different fluid resuscitation regimens during burn stage in swines

To explore the effects of different fluid resuscitation regimens on vascular permeability during burn stage in swines. A total of 24 Guangxi-BAMA miniature swines were numbered from 1 to 24 and randomly divided by EXCEL 2007 into 4 groups of succinylated gelatin, hydroxyethyl starch (HES 130/0.4), Parkland (lactated Ringer's solution) and allogeneic plasma (n = 6 each). The model of severe burn shock was established. And fluid resuscitation therapy was applied according to the established regimens of burn shock fluid resuscitation. The parameters of heart rate, blood pressure, urine volume, central venous pressure (CVP) and pulmonary capillary wedge pressure (PCWP) were recorded. Blood samples were collected prior to burns and at intervals of 4, 8, 24 and 48 h post-burns. The plasma colloidal osmotic pressure was measured. Evens blue was intravenously injected at 30 min before sacrificing. Then lung tissue samples were obtained and pulmonary vascular permeability index (PMPI) was measured. Statistical analyses were performed. All swines survived shock stage. The inter-group comparison revealed no statistical difference in heart rate, blood pressure, urine volume, CVP or PCWP. The plasma colloidal osmotic pressures (mmHg, 1 mmHg = 0.133 kPa) of four groups at each interval were as follows: (1) pre-burn: 25.4 ± 1.0, 25.9 ± 0.9, 25.5 ± 1.1, 25.0 ± 1.0; (2) 4 h: 24.3 ± 1.0, 25.6 ± 0.9, 13.2 ± 0.5, 25.0 ± 1.1; (3) 8 h: 23.3 ± 0.8, 25.2 ± 1.2, 12.7 ± 0.5, 24.0 ± 0.9; (4) 24 h: 22.0 ± 0.8, 23.1 ± 1.0, 12.4 ± 0.4, 23.3 ± 0.8; (5) 48 h: 22.3 ± 0.8, 24.1 ± 0.8, 18.1 ± 0.4, 23.5 ± 0.9. No statistically significant differences existed at the intervals of pre-burn between four groups (all P > 0.05). The HES 130/0.4 group at 8 h was significantly higher than that of allogeneic plasma group at the same interval (P < 0.05). The Parkland group at 4, 8, 24, 48 h were significantly lower than those of allogeneic plasma group (all P < 0.05). The succinylated gelatin group at 8, 24, 48 h, the HES 130/0.4 group at 8, 24, 48 h, the Parkland group at 4, 8, 24, 48 h and allogeneic plasma at 8, 24, 48 h decreased versus those at pre-burns (all P < 0.05). No statistically significant differences existed in pulmonary vascular permeability between the groups of succinylated gelatin (7.6 ± 0.9) µg/g, HES 130/0.4 (7.9 ± 1.8) µg/g, and allogeneic plasma (7.6 ± 1.2) µg/g, but all lower than the Parkland group (26.1 ± 2.3) µg/g (all P < 0.05). Natural colloid or artificial colloid (HES 130/0.4 or succinylated gelatin) have similar effects on vascular permeability in swines with severe burns during shock stage. Both are superior to the Parkland group.

The Use of Limited Fluid Resuscitation and Blood Pressure-Controlling Drugs in the Treatment of Acute Upper Gastrointestinal Hemorrhage Concomitant with Hemorrhagic Shock.

The aim of this study was to evaluate the usefulness of the limited fluid resuscitation regimen combined with blood pressure-controlling drugs in treating acute upper gastrointestinal hemorrhage concomitant with hemorrhagic shock. A total of 51 patients were enrolled and divided into a group that received traditional fluid resuscitation group (conventional group, 24 patients) and a limited fluid resuscitation group (study group, 27 patients). Before and after resuscitation, the blood lactate, base excess, and hemoglobin values, as well as the volume of fluid resuscitation and resuscitation time were examined. Compared with conventional group, study group had significantly better values of blood lactate, base excess, and hemoglobin (all p<0.05). In addition, both volume of fluid resuscitation and resuscitation time were significantly (p<0.05) lower in these patients. Limited fluid resuscitation combined with blood pressure-controlling drugs effectivelyxxx maintains blood perfusion of vital organs, improves whole body perfusion indicators, reduces the volume of fluid resuscitation, and achieves better bleeding control and resuscitation effectiveness.

Effects on ischemia-reperfusion injury with different fluid resuscitation regimens during burn shock stage in swines

To explore the effects on ischemia-reperfusion injury with different regimens of fluid resuscitation during severe burn shock stage in swines. A total of 24 Guangxi BA-MA mini-swine were numbered from 1 to 24 and randomly divided by EXCEL 2007 into 4 groups of succinylated gelatin, hydroxyethyl starch (HES 130/0.4), Parkland and allogeneic plasma (n = 6 each). Then the burn shock model was established. And fluid resuscitation therapy was applied according to the established regimens of burn shock fluid resuscitation. Blood samples were collected from the animals prior to burn injury and again at intervals of 4, 8, 24 and 48 hours post-injury. The levels of malondialdehyde, superoxide dismutase (SOD), xanthine oxidase (XOD) and total antioxidant capacity (T-AOC) were measured. And the results were analyzed statistically. Six swines within each group survived the shock stage and the outliers in detection index were eliminated. Then there were 5 swines in each group. The MDA of allogeneic plasma group at intervals of 8 hours was significantly lower than that of succinylated gelatin group, but higher than that of Parkland group [(3.46 ± 0.40) vs (4.55 ± 0.82), (2.59 ± 0.35) µmol/L, both P < 0.05]. The level of SOD had statistical difference at 48 hours between the HES 130/0.4 and allogeneic plasma groups ((72.55 ± 5.70) vs (65.42 ± 5.07) U/ml, P < 0.05). The level of XOD of the succinylated gelatin group at 4, 8 hour and they increased when compared to pre-burn ((12.00 ± 0.57), (11.28 ± 0.71) vs (9.12 ± 0.51) U/L, both P < 0.01).Statistical significance was observed at 4, 8 hours between succinylated gelatin and allogeneic plasma groups ((10.39 ± 1.24), (9.59 ± 1.17) U/L, both P < 0.01). The T-AOC of HES 130/0.4 group at 8 hours exceed the pre-burn ((2.06 ± 0.43) vs (1.30 ± 0.35) U/ml, P < 0.05). The allogeneic plasma group at 4, 8 hours showed increase when compared to pre-burn ((1.55 ± 0.37), (2.59 ± 0.60) vs (1.06 ± 0.13) U/ml, both P < 0.05). The succinylated gelatin group at 8, 48 hours decreased during the corresponding phase of allogeneic plasma group ((1.14 ± 0.26), (0.89 ± 0.20) vs (2.59 ± 0.60), (1.16 ± 0.20) U/ml, both P < 0.05). The comparison at 24, 48 hours between HES 130/0.4 and allogeneic plasma groups ((1.84 ± 0.41), (1.53 ± 0.21) vs (1.13 ± 0.35), (1.16 ± 0.20) U/ml) had statistical difference (both P < 0.01). The Parkland group at intervals of 8 hours was lower than that of allogeneic plasma group ((1.31 ± 0.19) vs (2.59 ± 0.60) U/ml, P < 0.01). HES130/0.4 and allogeneic plasma have comparable the parallel minimum damage effect on ischemia-reperfusion injury during burn shock stage are.

Uncontrolled hemorrhagic shock results in a hypercoagulable state modulated by initial fluid resuscitation regimens

Previous studies have shown large-volume resuscitation modulates coagulopathy and inflammation. Our objective was to analyze the effects of initial bolus fluids used in military and civilian settings on coagulation and inflammation in a prospective, randomized, blinded trial of resuscitation of uncontrolled hemorrhage. Fifty swine were anesthetized, intubated, and ventilated and had monitoring lines placed. A Grade V liver injury was performed followed by 30 minutes of hemorrhage. After 30 minutes, the liver was packed, and randomized fluid resuscitation was initiated during a 12-minute period with 2 L of normal saline, 2 L of lactated Ringer's solution, 250 mL of 7.5% saline with 3% Dextran, 500 mL of Hextend, or no fluid (NF). Animals were monitored for 2 hours after injury. Thrombelastograms (TEGs), prothrombin time (PT), partial thromboplastin time, fibrinogen as well as serum interleukin 6, interleukin 8, and tumor necrosis factor α levels were drawn at baseline and after 1 hour and 2 hours. The NF group had less posttreatment blood loss compared with other groups (p < 0.01). Blood loss was similar in the other groups. TEG R values in each group decreased from baseline at 1 and 2 hours (p < 0.02). The groups receiving 2 L of normal saline, 250 mL of 7.5% saline with 3% Dextran, or 500 mL of Hextend had lower TEG maximum amplitude values compared with NF group (p < 0.02). All fluids except lactated Ringer's solution resulted in significant increases in PT compared with NF, whereas all fluids resulted in significant decreases in fibrinogen compared with NF (p < 0.02). Fluid resuscitation groups as well as NF group demonstrated significant increases in inflammatory cytokines from baseline to 1 hour and baseline to 2 hours. There were no significant differences in inflammatory cytokines between groups at 2 hours. Withholding fluid resulted in the least significant change in PT, fibrinogen, and maximum amplitude and in the lowest posttreatment blood loss. Resuscitation with different initial fluid resuscitation strategies did not result in increased proinflammatory mediators compared with animals that did not receive fluid.

Microvascular and macrovascular flow are uncoupled in early polymicrobial sepsis

Microvascular dysfunction is considered to play an important pathophysiological role in sepsis. We addressed the hypothesis that macrovascular and microvascular flow are uncoupled in early sepsis, using a rodent model with well-characterized haemodynamic and biochemical markers of severity and subsequent mortality. Male Wistar rats received either an intraperitoneal injection of faecal slurry (sepsis, n=14) or sterile saline (sham, n=6). Identical i.v. fluid resuscitation regimens were administered 2 h later through tethered lines while conscious. At 6 h post-sepsis and in sham-operated controls, sidestream dark-field microvascular imaging of the left vastus lateralis muscle and transthoracic echocardiography were undertaken, again under anaesthesia. Non-operated rats (naive; n=5) served as negative controls. Mild and severe sepsis were defined a priori, based on the established predictive relationship between stroke volume and mortality in this model. Compared with sham-operated animals, there was a 19 (12-19)% and 62 (54-66)% decline in cardiac output in mild (n=8) and severe sepsis (n=6), respectively [median (inter-quartile range), P<0.0001]. Blinded assessment of microvascular imaging revealed that the microvascular flow index (MFI) was impaired in sepsis and in sham-operated controls (P<0.01), regardless of the degree of reduction in stroke volume and cardiac output. The MFI heterogeneity index revealed that only naive rats displayed a normal microvascular flow pattern. Microvascular flow is impaired during early sepsis and uncoupled from macrovascular function. The severity of macrovascular/cardiovascular compromise in early sepsis is not reflected by microvascular changes. Furthermore, surgery alone causes significant microvascular derangement, highlighting the importance of appropriate control subjects when using this technique.

Uncontrolled hemorrhagic shock results in a hypercoaguable state modulated by initial fluid resuscitation regimens

Uncontrolled hemorrhagic shock results in a hypercoaguable state modulated by initial fluid resuscitation regimens

The role of albumin as a resuscitation fluid for patients with sepsis: A systematic review and meta-analysis*

To assess whether resuscitation with albumin-containing solutions, compared with other fluids, is associated with lower mortality in patients with sepsis. MEDLINE, Embase, and Cochrane Central Register of Controlled Trials databases, the metaRegister of Controlled Trials, and the Medical Editors Trial Amnesty Register. Prospective randomized clinical trials of fluid resuscitation with albumin-containing solutions compared with other fluid resuscitation regimens, which included a population or subgroup of participants with sepsis, were included. Assessment of the validity of included studies and data extraction were conducted independently by two authors. For the primary analysis, the effect of albumin-containing solutions on all-cause mortality was assessed by using a fixed-effect meta-analysis. Seventeen studies that randomized 1977 participants were included in the meta-analysis. There were eight studies that included only patients with sepsis and nine where patients with sepsis were a subgroup of the study population. There was no evidence of heterogeneity, I² = 0%. The use of albumin for resuscitation of patients with sepsis was associated with a reduction in mortality with the pooled estimate of the odds ratio of 0.82 (95% confidence limits 0.67-1.0, p = .047). In this meta-analysis, the use of albumin-containing solutions for the resuscitation of patients with sepsis was associated with lower mortality compared with other fluid resuscitation regimens. Until the results of ongoing randomized controlled trials are known, clinicians should consider the use of albumin-containing solutions for the resuscitation of patients with sepsis.

Microcirculatory Parameters After Isotonic and Hypertonic Colloidal Fluid Resuscitation in Acute Hemorrhagic Shock

Volume resuscitation is one of the primary therapeutic goals in hemorrhagic shock, but data on microcirculatory effects of different colloidal fluid resuscitation regimen are sparse. We investigated sublingual mucosal microcirculatory parameters during hemorrhage and after fluid resuscitation with gelatin, hydroxyethyl starch, or hypertonic saline and hydroxyethyl starch in pigs. To induce hemorrhagic shock, 60% of calculated blood volume was withdrawn. Microvascular blood flow was assessed by laser Doppler velocimetry. Microcirculatory hemoglobin oxygen saturation was measured with a tissue reflectance spectrophotometry, and side darkfield imaging was used to visualize the microcirculation and to quantify the flow quality. Systemic hemodynamic variables, systemic acid base and blood gas variables, and lactate measurements were recorded. Measurements were performed at baseline, after hemorrhage, and after fluid resuscitation with a fixed volume regimen. Systemic hemodynamic parameters returned or even exceeded to baseline values in all three groups after fluid resuscitation, but showed significantly higher filling pressures and cardiac output values in animals treated with isotonic colloids. Microcirculatory parameters determined in gelatin and hydroxyethyl starch resuscitated animals, and almost all parameters except microvascular hemoglobin oxygen saturation in animals treated with hypertonic saline and hydroxyethyl starch, were restored after treatment. Hemorrhaged pigs can be hemodynamically stabilized with either isotonic or hypertonic colloidal fluids. The main finding is an adequate restoration of sublingual microcirculatory blood flow and flow quality in all three study groups, but only gelatin and hydroxyethyl starch improved microvascular hemoglobin oxygen saturation, indicating some inadequate oxygen supply/demand ratio maybe due to a better restoration of systemic hemodynamics in isotonic colloidal resuscitated animals.

Apoptosis and haemorrhagic shock

Abstract This is a review paper that provides an overview of current information on programmed cell death in haemorrhagic shock, including the identification of different molecular receptor signals. A PubMed search for all dates was undertaken using the search terms apoptosis, trauma and haemorrhagic shock. Original research, sentinel and review papers from peer-reviewed journals were included for identification of key concepts. Haemorrhagic shock remains a primary cause of death in civilian and military trauma. Apoptosis is accelerated following haemorrhagic shock. Many methods are used to detect and quantify apoptosis. Fluid resuscitation regimens vary in their effect on the extent of apoptosis. Investigators are examining the effects of haemorrhagic shock and fluid resuscitation on apoptotic signalling pathways. Molecular information is becoming available and being applied to the care of patients experiencing haemorrhagic shock, making it essential for nurses and other health care providers to consider the mechanisms and consequences of apoptosis.

Fluid resuscitation influences cardiovascular performance and mortality in a murine model of sepsis

Current murine models of sepsis do not account for the effects of aggressive fluid resuscitation on hemodynamics and mortality. Evaluate the impact of fluid resuscitation regimens on cardiovascular performance and survival in a murine model of sepsis. Mice (n = 90) were made septic by cecal ligation and puncture (CLP), and received antibiotics plus Low, Intermediate, or High fluid resuscitation regimens. Stroke volume (SV), cardiac output (CO), and fractional shortening (FS) were measured by echocardiography at predefined time points. Baseline echocardiographic measurements were similar in all groups. After CLP, SV and CO decreased early in all groups; High: 57.2 +/- 9.2 to 23.9 +/- 7.2 microL, and 26.8 +/- 4.9 to 13.1 +/- 5.8 ml/min; Intermediate: 52.1 +/- 7.0 to 21.5 +/- 6.6 microL, and 24.9 +/- 4.1 to 11.9 +/- 3.9 ml/min; Low: 54.0 +/- 7.0 to 20.3 +/- 5.6 microL, and 25.8 +/- 4.0 to 11.3 +/- 3.9 ml/min (P < 0.05 for all vs. baseline). With resuscitation there was a dose-dependent improvement in SV and CO (P < 0.05). At 24 h SV and CO were 44.0 +/- 13.8 microL and 20.7 +/- 8.5 ml/min in the High group, 39.8 +/- 12.3 microL and 16.7 +/- 6.5 ml/min in the Intermediate group, and 30.1 +/- 12.4 microL and 14.0 +/- 7.2 ml/min in the Low group. Survival was improved in the High fluid group (75%) compared to the Intermediate (58%) and the Low (35%) resuscitation groups (P < 0.05). In this model, as in human sepsis, the intensity of fluid resuscitation modulates hemodynamic response and mortality. Incorporation of early and aggressive fluid resuscitation can significantly enhances the clinical relevance of murine models of sepsis.

The Influence of the Type of Resuscitation Fluid on Gut Injury and Distant Organ Injury in a Rat Model of Trauma/Hemorrhagic Shock

Recognition that resuscitation with Ringers lactate (RL) potentiates trauma-hemorrhagic shock (T/HS)-induced organ injury and systemic inflammation has led to a search for improved initial fluid resuscitation regimens. However, one relatively neglected component in the search for new and novel resuscitation strategies is a determination of what fluid resuscitation therapy (i.e., control group) the new experimental regimen of interest should be tested against. Thus, we tested the effects of three commonly used resuscitation strategies on trauma-shock-induced gut and lung injury, as well as neutrophil activation and red blood cell (RBC) function. Male Sprague Dawley rats were subjected to a laparotomy (trauma) and 90 minutes of sham shock (trauma-sham shock [T/SS]) or a laparotomy plus hemorrhagic shock (T/HS), followed by a reperfusion period of 3 hours. The T/HS groups were resuscitated either with their shed blood (SB), or half the SB and 1.5 times the SB volume as RL (SB/RL), or 3 times the SB volume as RL (3RL). The T/SS groups received either no resuscitation or RL at 1.5 times the SB volume of the T/HS rats. Gut injury was quantified by measuring intestinal permeability to flourescein dextran (FD-4), as well as by histologic analysis of the terminal ileum. Lung injury was assessed histologically and by the magnitude of neutrophil sequestration as reflected in myeloperoxidase levels. Neutrophil activation was measured by quantitating the level of CD11b expression using flow cytometry. RBC injury was analyzed by measuring the RBC deformability. As compared with the T/SS groups, all three T/HS resuscitation regimens were associated with morphologic evidence of gut and lung injury, increased gut permeability, pulmonary leukosequestration, systemic neutrophil activation, and decreased RBC deformability (p < 0.05). However, the effect of the resuscitation regimens varied based on the tissues and cells tested. Morphologically, gut and lung injury as well as pulmonary neutrophil sequestration was worse in the 3RL T/HS group than the other two T/HS groups. As compared with the other two T/HS resuscitation regimens, resuscitation with the SB/RL combination was associated with less of an increase in gut permeability, systemic neutrophil activation, and RBC rigidification (p < 0.05). The type of resuscitation regimen used influenced the extent of organ injury and cellular activation or dysfunction observed after T/HS with different resuscitation regimens showing varying effects depending on the cell or organ tested. Thus, when testing novel fluid resuscitation regimen, attention must be paid to the control resuscitation regimen used.

HIGH-DOSE VITAMIN C INFUSION REDUCES FLUID REQUIREMENTS IN THE RESUSCITATION OF BURN-INJURED SHEEP

Fluid resuscitation to maintain adequate tissue perfusion while reducing edema in the severely burned patient remains a challenge. Recent studies suggest that reactive oxygen species generated by thermal injury are involved in edema formation associated with burn. The present study tested the hypothesis that adding a free radical scavenger to the resuscitation fluid would reduce total fluid requirements in the treatment of severe thermal injury. Anesthetized chronically instrumented sheep received a 40% total body surface area full-thickness flame burn. At 1 h after injury, animals were resuscitated with lactated Ringer's (LR, n = 14) as control, LR containing high doses of vitamin C (VC, n = 6), 1000 mOsM hypertonic saline (HS, n = 7), or 1000 HS containing VC (HS/VC, n = 7) in coded bags so that investigators were blinded to the treatment. Fluids were infused at an initial Parkland rate of 10 mL/kg/h, adjusted hourly to restore and maintain urine output at 1 to 2 mL/kg/h. Sheep in the VC or HS/VC group received 250 mg/kg VC in the first 500 mL of LR or HS, and then 15 mg/kg/h thereafter. Hemodynamic variables and indices of antioxidant status were measured. At 48 h postburn, sheep were euthanized, and heart, liver, lung, skeletal muscle, and ileum were evaluated for antioxidant status. All fluid resuscitation regimens were equally effective in restoring cardiac output to near baseline levels; no treatment effects were apparent on arterial pressure or heart rate. VC infusion significantly reduced fluid requirements and, therefore, net fluid balance (fluid in, urine out) by about 30% at 6 h and about 50% at 48 h in comparison with the LR group (P < 0.05). HS and HS/VC reduced fluid requirements by 30% and 65%, respectively, at 6 h, but the volume-sparing effect of HS was not observed after 36 h and that of HS/VC was lost after 12 h. Plasma total antioxidant potential increased about 25-fold (P < 0.05) at 2 and 3 h in response to VC infusion compared with the LR and HS groups, and remained about 5- to 10-fold higher throughout the rest of the study. VC infusion also prevented the 4-fold increase in plasma thiobarbituric acid reactive substances seen in the LR group early after burn (P < 0.05). Tissue antioxidant status was similar between groups. In this sheep burn model, continuous high-dose VC infusion reduced net fluid balance, reduced indices of plasma lipid peroxidation, and maintained overall antioxidant status in comparison with standard-of-care LR treatment.

Prehospital Management and Fluid Resuscitation in Hypotensive Trauma Patients Admitted to Karolinska University Hospital in Stockholm

Few previous studies have been conducted on the prehospital management of hypotensive trauma patients in Stockholm County. The aim of this study was to describe the prehospital management of hypotensive trauma patients admitted to the largest trauma center in Sweden, and to assess whether prehospital trauma life support (PHTLS) guidelines have been implemented regarding prehospital time intervals and fluid therapy. In addition, the effects of the age, type of injury, injury severity, prehospital time interval, blood pressure, and fluid therapy on outcome were investigated. This is a retrospective, descriptive study on consecutive, hypotensive trauma patients (systolic blood pressure < or = 90 mmHg on the scene of injury) admitted to Karolinska University Hospital in Stockholm, Sweden, during 2001-2003. The reported values are medians with interquartile ranges. Basic demographics, prehospital time intervals and interventions, injury severity scores (ISS), type and volumes of prehospital fluid resuscitation, and 30-day mortality were abstracted. The effects of the patient's age, gender, prehospital time interval, type of injury, injury severity, on-scene and emergency department blood pressure, and resuscitation fluid volumes on mortality were analyzed using the exact logistic regression model. In 102 (71 male) adult patients (age > or = 15 years) recruited, the median age was 35.5 years (range: 27-55 years) and 77 patients (75%) had suffered blunt injury. The predominant trauma mechanisms were falls between levels (24%) and motor vehicle crashes (22%) with an ISS of 28.5 (range: 16-50). The on-scene time interval was 19 minutes (range: 12-24 minutes). Fluid therapy was initiated at the scene of injury in the majority of patients (73%) regardless of the type of injury (77 blunt [75%] / 25 penetrating [25%]) or injury severity (ISS: 0-20; 21-40; 41-75). Age (odds ratio (OR) = 1.04), male gender (OR = 3.2), ISS 21-40 (OR = 13.6), and ISS >40 (OR = 43.6) were the significant factors affecting outcome in the exact logistic regression analysis. The time interval at the scene of injury exceeded PHTLS guidelines. The vast majority of the hypotensive trauma patients were fluid-resuscitated on-scene regardless of the type, mechanism, or severity of injury. A predefined fluid resuscitation regimen is not employed in hypotensive trauma victims with different types of injuries. The outcome was worsened by male gender, progressive age, and ISS > 20 in the exact multiple regression analysis.

Tissue Oxygenation in Sepsis

The effect of sepsis on tissue oxygenation is complex and often confusing. This is in part due to the paucity of data from patients (excluding whole-body studies), and in part to the huge variation in laboratory models which have utilised different species, organs and cell lines, different insults, study durations and methods, fluid resuscitation regimens, and end-points. An organ-variable redistribution in microvascular flow undoubtedly occurs though its significance in causing tissue hypoxia remains questionable. A lower oxygen consumption is recognised in patients with an increasing severity of sepsis, with a better prognosis being seen in those spontaneously achieving higher values of global oxygen delivery and consumption. However, septic patients and (well-resuscitated) animal models demonstrate an increase in tissue oxygen tension. This suggest adequate delivery but impaired utilisation of oxygen. As over 90% of oxygen consumed by the body is for mitochondrial generation of ATP by oxidative phosphorylation, a cellular defect is strongly implicated. Mitochondrial dysfunction has been inconsistently demonstrated; on closer inspection, short-term and/or ‘milder’ insult models often show no change or an increase in mitochondrial activity whereas the longer duration and/or more severe models show depressed function. This is borne out by preliminary human studies. Reactive oxygen and nitrogen species appear instrumental in causing this dysfunction; they may also act as signalling mediators for cellular ‘shutdown’, possibly as a protective mechanism to reduce ATP turnover in the face of a decrease in production.