Models for blood component and fluid administration

Chapter 134 - Components of Fluid Balance and Monitoring

Treatment of haemorrhagic shock involves maintaining blood pressure and tissue perfusion until bleeding is controlled. Different resuscitation strategies have been used to maintain the blood pressure in trauma patients until bleeding is controlled. However, while maintaining blood pressure may prevent shock, it may worsen bleeding. To assess the effects of early versus delayed, and larger versus smaller volume of fluid administration in trauma patients with bleeding. We searched the Cochrane Controlled Trials Register, the specialised register of the Injuries Group, MEDLINE, EMBASE, the National Research Register and the Science Citation Index. We checked reference lists of identified articles and contacted authors and experts in the field. Randomised trials of the timing and volume of intravenous fluid administration in trauma patients with bleeding. Trials in which different types of intravenous fluid were compared were excluded. Two reviewers independently extracted data and assessed trial quality. We did not combine the results quantitatively because the interventions and patient populations were so diverse. Early versus delayed fluid administration. Three trials reported mortality and two coagulation data. In the first trial (n=598) relative risk (RR) for death with early fluid administration was 1.26 (95% confidence interval of 1.00-1.58). The weighted mean differences (WMD) for prothrombin time and partial thromboplastin time were 2.7 (95% CI 0.9-4.5) and 4.3 (95% CI 1.74-6.9) seconds respectively. In the second trial (n=50) RR for death with early blood transfusion was 5.4 (95% CI 0.3-107.1). The WMD for partial thromboplastin time was 7.0 (95% CI 6.0-8.0) seconds. In the third trial (n=1309) RR for death with early fluid administration was 1.06 (95% CI 0.77-1.47). Larger versus smaller volume of fluid administration. Three trials reported mortality and one coagulation data. In the first trial (n=36) RR for death with a larger volume of fluid resuscitation was 0.80 (95% CI 0.28-22.29). Prothrombin time and partial thromboplastin time were 14.8 and 47.3 seconds in those who received a larger volume of fluid, as compared to 13.9 and 35.1 seconds in the comparison group. In the second trial (n=110) RR for death with a high systolic blood pressure resuscitation target (100mmHg) maintained with a larger volume of fluid, as compared to low systolic blood pressure resuscitation target (70mmHg) maintained with a smaller volume of fluid was 1.00 (95% CI 0.26-3.81). In the third trial (n=25) there were no deaths. We found no evidence from randomised controlled trials for or against early or larger volume of intravenous fluid administration in uncontrolled haemorrhage. There is continuing uncertainty about the best fluid administration strategy in bleeding trauma patients. Further randomised controlled trials are needed to establish the most effective fluid resuscitation strategy.

Excessive drinking and drunkenness are tightly linked to many types of intentional and unintentional injuries involving trauma and blood loss, which often necessitate emergency medical intervention. This article considers the impact of trauma, massive blood loss, and the administration of life-saving replacement fluids on a person's blood alcohol concentration (BAC) and rate of ethanol metabolism. Both German and English language journals were reviewed and results from animal experiments, human studies, and actual victims of trauma undergoing life-saving treatment were considered. If trauma-related bleeding occurs when some ingested alcohol remains unabsorbed in the stomach, then under these circumstances continued absorption into portal venous blood is delayed, owing to altered splanchnic circulation. Hemodilution caused by administration of replacement fluids has only minimal effects on a preexisting BAC, because ethanol distributes into the total body water (TBW) compartment, which represents 50-60% of body weight. After hypovolemia there is a transfer of fluids from tissue compartments into the blood, which becomes more like plasma in composition with lower hematocrit and hemoglobin content. Unless the trauma or emergency treatment impedes hepatic blood flow, the rate of ethanol metabolism is not expected to differ from normal values, namely 0.10-0.25 g/L/h (0.01-0.025 g% per h). If ethanol is fully absorbed and distributed in all body fluids and tissues, neither massive blood loss nor administration of resuscitating fluids is expected to have any significant effect on a preexisting BAC or the rate of ethanol metabolism.

BackgroundTranexamic acid (TXA) has been routinely delivered in multisegmental spinal decompression and bone graft fusion surgeries with satisfactory outcomes in minimizing gross blood loss and transfusion demands. However, concerns remain that intravenously delivered TXA (ivTXA) may increase risks of postoperative convulsive seizures and systemic thrombogenicity. Topical use of TXA (tTXA), being more targeted to the surgical bleeding site while minimizing patient systemic exposure to ivTXA, has been successfully applied to attenuate blood losses and transfusion requirements in hip and knee arthroplasty. Yet, randomized controlled trials on tTXA efficacy and safety are still lacking in spinal surgeries. With this knowledge gap, we hypothesize that tTXA exhibits non-inferiority to ivTXA in blood conservation and clinical safety in multisegmental spinal decompression and bone graft fusion surgeries.MethodsA prospective, randomized, double-blind, non-inferiority study design will be adopted. The target sample size is 176. Eligible patients will be randomly allocated to receive either ivTXA or tTXA treatment. The primary end point is the perioperative total blood loss. Secondary end points consist of visible blood losses (intraoperative, postoperative 0–24 h, postoperative 0–48 h, combined perioperative blood loss, total postoperative blood loss), postoperative hidden blood loss, plasma TXA levels, postoperative conventional coagulation monitoring (prothrombin time, activated partial thromboplastin time, fiber Bragg grating, international normalized ratio), postoperative thromboelastography monitoring (reaction time, clot formation time, clot strength, fibrinolysis), postoperative hemoglobin nadir (within postoperative 48 h), perioperative transfusion amounts and rates, and length of hospital stay. Safety end points will be monitored too.DiscussionThis proposed study will contribute to expanding clinical evidences of tTXA for bleeding management in major spinal surgeries. This will be a high-quality prospective randomized trial with sufficient sample size, strict methodology, and few design deficits. It will investigate the potentiality of tTXA as an alternative to ivTXA in improving the current standard of care in multisegmental spinal surgeries, thereby optimizing the enhanced recovery after surgery scheme in spinal surgeries.Trial registrationClinicalTrials.gov, NCT03011866. Registered on 5 January 2017.

Aim: to justify a differentiated approach to the treatment of obstetric coagulopathic bleeding depending on the nature of hemostasis disorders.Materials and Methods. A prospective cohort study was conducted involving 52 patients with postpartum hemorrhage (PPH) who gave a child birth between 2021 and 2023. Diagnostics and treatment of coagulopathy was carried out according to the algorithm using thromboelastometry (TEM) parameters. Patients were divided into 3 groups depending on blood loss volume: group 1 (n = 19) – blood loss up to 1499 ml; group 2 (n = 14) – blood loss from 1500 to 1999 ml; group 3 (n = 19) – blood loss 2000 ml and more. The following hemostasis parameters were determined: platelet count, prothrombin index, activated partial thromboplastin time (APTT), Claus fibrinogen level, international normalized ratio, and TEM parameters, including clotting time (CT), clot formation time (CFT), maximum clot firmness (MCF), and maximum clot firmness at 10 minutes (A10) on the EXTEM channels (a test in which recombinant tissue factor is used to activate the extrinsic coagulation pathway), FIBTEM (a test in which platelet activity is suppressed by cytochalasin D, which allows detecting fibrinogen deficiency or qualitative disturbances in fibrin polymerization), and INTEM (a test in which ellagic acid is used as a contact activator of the intrinsic coagulation pathway). Blood samples were collected before administration of blood components and products, tranexamic acid.Results. Statistically significant differences were found for the fibrinogen level, MCF and A10 parameters on the FIBTEM channel depending on blood loss volume (p < 0.05), indicating a decrease in the quality of fibrin clot upon with increasing blood loss. Highly tight direct relationships were found between the fibrinogen, MCF and A10 values, demonstrating that with a decrease in the fibrinogen level at the time of bleeding by 1.0 g/L, a decrease in MCF by 3.802 mm (the resulting model explains 64.3 % of the observed variance), and A10 by 3.497 mm (the resulting model explains 64.1 % of the observed variance) should be expected. All patients whose blood loss volume reached 2000 ml and more were administered cryoprecipitate, the differences in the parameters were statistically significant between group 3 vs. group 1 and group 2 (p < 0.001). TEM parameters CT and CFT on the INTEM channel also correlated with blood loss volume and had a significant direct correlation between noticeable tightness (according to the Chaddock scale) between APTT and CT (ρ = 0.612; p < 0.001) as well as moderate tightness between APTT and CFT (rxy = 0.44; p = 0.017). The need for transfusion of fresh frozen plasma (FFP) and prothrombin complex concentrates (PCСs) arose with APTT more than 35 seconds in 77 % of cases (among all patients), with the CT parameter more than 260 seconds – in 63 % of cases and CFT more than 110 sec – in 63 % of cases, respectively; the differences in the indicators are significant while compared with those of patients requiring no introduction of FFP and PPC (p < 0.05). Based on controlled transfusion protocol, in group 1, in 57.9 % of cases it was possible apply no transfusion therapy; the differences in indicators are significant while comparing group 2 and group 3 (p < 0.05).Conclusion. The use of the TEM method in the diagnostics of hemostasis disorders with PPH allowed for the differential and short-term application of pathogenetically justified therapy with blood components and preparations only in cases where it was required.

Sepsis, the leading cause of death among critically ill patients worldwide, can induce sepsis-induced cardiomyopathy (SICM), which is characterized by reversible acute impairment of biventricular systolic and diastolic functions. SICM has a high incidence in sepsis patients and significantly increases mortality, and it has emerged as one of the key factors contributing to death in septic shock.[1] The pathological manifestations of SICM are highly heterogeneous, encompassing various forms such as left ventricular systolic dysfunction and diastolic dysfunction, which pose significant challenges to early identification and treatment. Fluid resuscitation serves as the cornerstone of sepsis treatment, yet there remains ongoing controversy regarding its optimal volume and timing.[2] Meanwhile, mechanical circulatory support technologies such as venoarterial extracorporeal membrane oxygenation (VA-ECMO) have been successfully applied in refractory septic shock.[3] These 2 approaches exert a synergistic effect based on complementary hemodynamic regulation mechanisms. Fluid resuscitation optimizes preload to improve cardiac filling while mechanical support directly replaces cardiac pump function to reduce afterload. This bidirectional regulation is particularly crucial in patients with mixed shock (septic combined with cardiogenic) as it helps resolve the contradiction between fluid resuscitation and diuretic therapy.[4] In current clinical practice, controversies including the lack of individualized volume standards for fluid resuscitation, no consensus on the timing of mechanical support intervention, and difficulties in balancing fluid administration and diuresis in mixed shock states highlight the evidence gap in this field and the urgency for further research. The pathogenesis of SICM involves multiple molecular abnormalities, such as the release of inflammatory mediators, mitochondrial dysfunction, and calcium homeostasis imbalance. Mechanisms like toll-like receptor-mediated pyroptosis further exacerbate myocardial injury, ultimately leading to hemodynamic changes, including reduced cardiac output and ventricular dilatation.[5] The hemodynamic effects of fluid resuscitation exhibit a double-edged sword property. During the initial phase, fluid infusion increases preload to enhance cardiac output, but excessive resuscitation can exceed the compensatory range of the Frank–Starling curve. This not only aggravates myocardial oxygen consumption and interstitial edema but may also worsen right heart dysfunction.[2] Among mechanical circulatory support modalities, VA-ECMO exerts a compensatory role by maintaining systemic perfusion pressure, reducing cardiac workload, and protecting end-organ perfusion. It is more suitable for patients with biventricular dysfunction compared with venovenous-ECMO, though it may also introduce new challenges, such as increased left ventricular afterload.[6] Evidence-based studies indicate that lactated Ringer’s solution may be superior to normal saline for initial resuscitation.[7] After the implantation of mechanical circulatory support devices, dynamic indicators such as stroke volume variation should be used to assess fluid responsiveness, and hemodynamic parameters should be interpreted in conjunction with a multiparameter monitoring system.[8] Treatment timing directly affects prognosis. Early fluid resuscitation within 8 hours of onset can improve mortality, but large-volume resuscitation may increase risks when mechanical ventilation resources are limited. The association between SICM and mortality, as well as its dynamic changes, also needs to be incorporated into prognostic assessments.[9] Currently, the treatment of SICM still lacks high-quality evidence-based individualized protocols. Key issues such as the optimal support strategy for different hemodynamic subgroups and the balance between fluid administration and diuresis in mixed shock states remain unclear.[4] Precision therapy guided by biomarkers is limited by insufficient mechanistic research. For instance, the mechanisms underlying the impact of diabetes on SICM have not been fully elucidated.[10] Monitoring technologies face multiple bottlenecks. The predictive value of traditional parameters decreases during mechanical circulatory support, and there is a lack of bedside quantitative tools for assessing microcirculatory function.[8] Multicenter studies have poor result comparability due to inconsistent definitions of SICM and varied resource accessibility, and most evidence comes from single-center studies with insufficient follow-up on long-term cardiac function recovery.[11] Future efforts should focus on developing intelligent decision support systems that integrate multimodal data to resolve contradictions in mixed shock treatment and optimize the judgment of optimal intervention timing for mechanical support. They should also explore biomarker combinations that distinguish pathological subtypes to guide the prediction of fluid resuscitation response and sequential application of treatments. Additionally, studies on the timing optimization of mechanical support and pharmacotherapy are needed to clarify the microcirculatory effects of different support modalities and the principles of fluid management after device implantation.[2] At the same time, unified diagnostic criteria for SICM should be established to reduce research heterogeneity. Conflict of interest statement The authors declare no conflict of interest. Author contributions Meng C and Sun J conducted searches of the scientific literature and developed the draft of the manuscript. Miao G provided contributions to the conception and design of the study, in addition to revising the manuscript with a focus on critical intellectual content. All authors reviewed and approved the final version of the manuscript. Funding This study was funded by the National Key R&D Program of China (2023YFC3011904). Ethical approval of studies and informed consent Not applicable. Acknowledgements None.

Background Sepsis is an inflammatory response to severe infection characterized by hypovolemia and vasodilation and treated with early antibiotics and fluid resuscitation. In-hospital mortality rates have decreased from 80% in the early years of intensive care to 20-30% in the modern era through improved surveillance, early treatment of underlying infection, and advances in support for failing organs. Despite the central role intravenous (IV) fluid administration has played in sepsis management for the last 15 years, fundamental questions regarding “which fluid” and “in what amount” remain unanswered. Objective To compare between the outcomes of fluid administration strategies in the form of restricted or usual fluid administration in patient with severe sepsis and septic shock, and to detect the optimal strategy of fluid administration which decreases morbidity and mortality. Patients and Methods This was a Prospective controlled; randomized, comparative study was conducted in the intensive care units at Ain-Shams University Hospitals and Gamal Abdelnaser Hospital. This study was conducted on 80 adult patients divided into two groups: Group A: 40 adult patients taking the Usual Care, and Group B: 40 adult patients taking the Restrictive Care. Results The restrictive fluid group received significantly less resuscitative IV fluid than the usual care group prior to randomization, over 24 hours, over 48 hours, over 72 hours and total, Moreover; the restrictive fluid group also received a lower fraction of non-resuscitative IV fluid than the usual care group. In addition, the restrictive fluid group also received less amount of total forms IV fluid than the usual care group. There were no statistically significant differences between the two groups in adjunct resuscitative measures administered including albumin, blood transfusion, or stress dose steroids. By day 30, 9 participants (22.5%) in the restrictive fluid group and 7 participants (17.5%) in the usual care had died with no statistical significant difference between the both groups (p = 0.29). Conclusion A restrictive resuscitation strategy that significantly limited the amount of IV fluid administered to patients with severe sepsis and septic shock show slight improvement as regard mean arterial blood pressure, urine output and lactate level. at the same time did not appear to increase mortality, organ dysfunction, or adverse events. Our data contribute to the current state of clinical equipoise surrounding the use of IV fluids in sepsis, support a larger multicenter trial addressing this topic, and inform future study design. This study demonstrates that a restrictive resuscitation strategy can successfully reduce the amount of IV fluid administered to patients with severe sepsis and septic shock compared with usual care. Although limited by the sample size, we observed no increase in mortality, organ failure, or adverse events.

The fluid resuscitation needs of children with small area burns are difficult to predict. The authors hypothesized that a novel computational algorithm called the compensatory reserve index (CRI), calculated from the photoplethysmogram waveform, would correlate with percent total body surface area (%TBSA) and fluid administration in children presenting with ≤20% TBSA burns. The authors recorded photoplethysmogram waveforms from burn-injured children that were later processed by the CRI algorithm. A CRI of 1 represents supine normovolemia; a CRI of 0 represents the point at which a subject is predicted to experience hemodynamic decompensation. CRI values from the first 10 minutes of monitoring were compared to clinical data. Waveform data were available for 27 children with small to moderate sized burns (4-20 %TBSA). The average age was 6.3 ± 1.1 years, the average %TBSA was 10.4 ± 0.8%, and the average CRI was 0.36 ± 0.03. CRI inversely correlated with the %TBSA (P < .001). Twenty children were transferred with an average reported %TBSA of 16.5 ± 1.4%, which was significantly higher than the actual %TBSA (P < .001). CRI correlated better with actual %TBSA compared to reported %TBSA (P = .02). CRI correlated with the amount of fluid resuscitation given at the time of CRI measurement (P = .02) and was inversely related to total fluids given per 24 hours for children with adequate urine output (>0.5 ml/kg/hr) (P < .001). The CRI is decreased in children with small to moderate size burns, and correlates with %TBSA and fluid administration. This suggests that the CRI may be useful for fluid resuscitation guidance, warranting further study.

Crossing the rubicon: Exploring different peri – Operative fluid resuscitation strategies in traumatic extremity free tissue transfer- a retrospective case control study

Intravenous fluids are widely administered in the ICU with the intention of preventing or ameliorating acute kidney injury (AKI). This review focuses on recent studies examining fluid administration and renal function in critical illness to critically examine conventional justifications for fluid administration. Early, targeted, resuscitation of inadequate cardiac output in shock may have a beneficial effect on organ function and patient outcome. However, experimental evidence suggests the relationship between fluid administration and an increase in renal oxygen delivery is weak, whereas any beneficial effects from fluid administration can be short lived. Conversely, evidence associating fluid overload and adverse outcomes is strengthening, whereas more restrictive fluid administration does not seem to predispose to clinically significant AKI in many situations. Furthermore, concerns persist that some colloid or high chloride concentration solutions may directly impair renal function independent of volume overload. Adequate volume resuscitation remains a cornerstone to the emergent treatment of critical illness. However, continued fluid administration and positive fluid balances have not been shown to improve renal outcomes and may worsen overall prognosis in AKI. Concerns about renal dysfunction should not deter clinicians from adopting more restrictive approaches to fluid administration.

We thank you for your comments. The American Academy of Pediatrics Subcommittee on Fluid and Electrolyte Therapy has spent >2 years of hard work on this guideline.We agree with Drs Segar and Brophy that appropriate fluid volumes for pediatric patients who are hospitalized are both important and understudied. In the guideline, we did not specifically address the volume of intravenous fluids (IVFs) because there was insufficient literature for us to do so. In the guideline, we also specifically excluded both fluid overload and polyuric states in which IVF volumes would need to be either restricted or liberalized, respectively. In our review of the literature, authors of 2 studies1 directly compared different rates of fluid administration, and no differences in hyponatremia were observed. It appears that fluid type is more important than fluid rate for the outcome of hyponatremia; however, more research needs to be done.We concur that the amount of sodium infused in maintenance IVFs is higher than usual dietary requirements. However, this is also true of IVFs with 0.33% or 0.45% saline. The amount of sodium and water delivered to an infant or child receiving isotonic maintenance fluids is proportionally the same as that of an adult when expressed in relation to body surface area. Our literature review, as noted in the guideline, did not reveal hypernatremia or volume overload from isotonic fluid administration. Neither hypernatremia nor volume overload would be expected, however, because normal-functioning kidneys can generate free water by excreting a hypertonic urine, and this is a common occurrence in the ambulatory setting.2As described in our limitations of the recommendation, the use of isotonic fluids when maintenance IVFs are required does not mean that there are no indications for administering hypotonic fluids or that isotonic fluids will be safe in all patients. The clinical assessment of each patient is necessary to determine the appropriate parenteral or enteral prescription, with specific attention to volume administered, type of solution, and biochemical monitoring.The practice guideline published is not the end but the start of the conversation. We need to do more work, ask more questions, educate each other, and get more answers about this issue. We need to be more thoughtful about each of our patients and avoid reflexive practice.

The haemostatic status of dogs with canine parvovirus (CPV) enteritis, within 24 h of admission after initial fluid administration, has been described previously, but the haemostatic status at admission and after standard fluid resuscitation, as well as after initial fluid redistribution, has not been investigated previously. The objective of this study was to characterise the haemostatic status at admission and describe the effect of crystalloid fluid resuscitation on haemostatic variables in dogs with CPV enteritis. Twenty-seven client-owned, hospitalised dogs with confirmed natural CPV infection and 15 healthy age-matched controls were included in a prospective, observational clinical study. The volume of resuscitation fluid, haematocrit (HCT), platelet count, thromboelastography (TEG) variables, antithrombin (AT) activity, fibrinogen- and C-reactive protein (CRP) concentrations were measured in all dogs at admission, after fluid resuscitation and, in 10 dogs, after receiving an additional 3 hours of maintenance-rate crystalloid fluids. For the CPV group at admission, the median TEG reaction time (R) and maximum amplitude (MA) or clot strength, as well as the median HCT, fibrinogen and CRP concentrations, were significantly increased compared to the controls. After fluid resuscitation, median R was significantly shorter, MA significantly increased and HCT and AT activity significantly decreased compared to admission values. The haemostatic variables remained unchanged after 3 h of maintenance-rate crystalloid therapy. The increased clot strength present in dogs with CPV enteritis at admission was exacerbated after fluid resuscitation and persisted for hours after large-volume crystalloid fluid administration.

Rational Fluid Resuscitation in Sepsis for the Hospitalist: A Narrative Review

HIGH oxygen content within the plasma that can supplement, or even supplant, the hemoglobin-bound oxygen can be achieved by use of hyperbaric oxygen administration. In 1960, Boerema et al. 1 exsanguinated pigs and then reanimated them by treatment in a hyperbaric chamber, Forty years later, hyperbaric therapy can be life saving when used as temporizing or definitive therapy in cases of severe anemia when transfusion is difficult to achieve or refused.

BackgroundPostpartum hemorrhage (PPH) is associated with maternal morbidity and mortality and has an increasing incidence in high-resource countries, despite dissemination of guidelines, introduction of skills training, and correction for risk factors. Current guidelines advise the administration, as fluid resuscitation, of almost twice the amount of blood lost. This advice is not evidence-based and could potentially harm patients.MethodsAll women attending the outpatient clinic who are eligible will be informed of the study; oral and written informed consent will be obtained. Where there is more than 500 ml blood loss and ongoing bleeding, patients will be randomized to care as usual, fluid resuscitation with 1.5–2 times the amount of blood loss or fluid resuscitation with 0.75–1.0 times the blood loss. Blood loss will be assessed by weighing all draping. A blood sample, for determining hemoglobin concentration, hematocrit, thrombocyte concentration, and conventional coagulation parameters will be taken at the start of the study, after 60 min, and 12–18 h after delivery. In a subgroup of women, additional thromboelastometric parameters will be obtained.DiscussionOur hypothesis is that massive fluid administration might lead to a progression of bleeding due to secondary coagulation disorders. In non-pregnant individuals with massive blood loss, restrictive fluid management has been shown to prevent a progression to dilution coagulopathy. These data, however, cannot be extrapolated to women in labor.Our objective is to compare both resuscitation protocols in women with early, mild PPH (blood loss 500–750 ml) and ongoing bleeding, taking as primary outcome measure the progression to severe PPH (blood loss > 1000 ml).Trial registrationNetherlands Trial Register, NTR 3789. Registered on 11 January 2013.