Clinical symptoms, signs and tests for identification of impending and current water-loss dehydration in older people.

BACKGROUND: There is evidence that water-loss dehydration is common in older people and associated with many causes of morbidity and mortality. However, it is unclear what clinical symptoms, signs and tests may be used to identify early dehydration in older people, so that support can be mobilised to improve hydration before health and well-being are compromised. OBJECTIVES: To determine the diagnostic accuracy of state (one time), minimally invasive clinical symptoms, signs and tests to be used as screening tests for detecting water-loss dehydration in older people by systematically reviewing studies that have measured a reference standard and at least one index test in people aged 65 years and over. Water-loss dehydration was defined primarily as including everyone with either impending or current water-loss dehydration (including all those with serum osmolality ≥ 295 mOsm/kg as being dehydrated). SEARCH METHODS: Structured search strategies were developed for MEDLINE (OvidSP), EMBASE (OvidSP), CINAHL, LILACS, DARE and HTA databases (The Cochrane Library), and the International Clinical Trials Registry Platform (ICTRP). Reference lists of included studies and identified relevant reviews were checked. Authors of included studies were contacted for details of further studies. SELECTION CRITERIA: Titles and abstracts were scanned and all potentially relevant studies obtained in full text. Inclusion of full text studies was assessed independently in duplicate, and disagreements resolved by a third author. We wrote to authors of all studies that appeared to have collected data on at least one reference standard and at least one index test, and in at least 10 people aged ≥ 65 years, even where no comparative analysis has been published, requesting original dataset so we could create 2 x 2 tables. DATA COLLECTION AND ANALYSIS: Diagnostic accuracy of each test was assessed against the best available reference standard for water-loss dehydration (serum or plasma osmolality cut-off ≥ 295 mOsm/kg, serum osmolarity or weight change) within each study. For each index test study data were presented in forest plots of sensitivity and specificity. The primary target condition was water-loss dehydration (including either impending or current water-loss dehydration). Secondary target conditions were intended as current (> 300 mOsm/kg) and impending (295 to 300 mOsm/kg) water-loss dehydration, but restricted to current dehydration in the final review.We conducted bivariate random-effects meta-analyses (Stata/IC, StataCorp) for index tests where there were at least four studies and study datasets could be pooled to construct sensitivity and specificity summary estimates. We assigned the same approach for index tests with continuous outcome data for each of three pre-specified cut-off points investigated.Pre-set minimum sensitivity of a useful test was 60%, minimum specificity 75%. As pre-specifying three cut-offs for each continuous test may have led to missing a cut-off with useful sensitivity and specificity, we conducted post-hoc exploratory analyses to create receiver operating characteristic (ROC) curves where there appeared some possibility of a useful cut-off missed by the original three. These analyses enabled assessment of which tests may be worth assessing in further research. A further exploratory analysis assessed the value of combining the best two index tests where each had some individual predictive ability. MAIN RESULTS: There were few published studies of the diagnostic accuracy of state (one time), minimally invasive clinical symptoms, signs or tests to be used as screening tests for detecting water-loss dehydration in older people. Therefore, to complete this review we sought, analysed and included raw datasets that included a reference standard and an index test in people aged ≥ 65 years.We included three studies with published diagnostic accuracy data and a further 21 studies provided datasets that we analysed. We assessed 67 tests (at three cut-offs for each continuous outcome) for diagnostic accuracy of water-loss dehydration (primary target condition) and of current dehydration (secondary target condition).Only three tests showed any ability to diagnose water-loss dehydration (including both impending and current water-loss dehydration) as stand-alone tests: expressing fatigue (sensitivity 0.71 (95% CI 0.29 to 0.96), specificity 0.75 (95% CI 0.63 to 0.85), in one study with 71 participants, but two additional studies had lower sensitivity); missing drinks between meals (sensitivity 1.00 (95% CI 0.59 to 1.00), specificity 0.77 (95% CI 0.64 to 0.86), in one study with 71 participants) and BIA resistance at 50 kHz (sensitivities 1.00 (95% CI 0.48 to 1.00) and 0.71 (95% CI 0.44 to 0.90) and specificities of 1.00 (95% CI 0.69 to 1.00) and 0.80 (95% CI 0.28 to 0.99) in 15 and 22 people respectively for two studies, but with sensitivities of 0.54 (95% CI 0.25 to 0.81) and 0.69 (95% CI 0.56 to 0.79) and specificities of 0.50 (95% CI 0.16 to 0.84) and 0.19 (95% CI 0.17 to 0.21) in 21 and 1947 people respectively in two other studies). In post-hoc ROC plots drinks intake, urine osmolality and axillial moisture also showed limited diagnostic accuracy. No test was consistently useful in more than one study.Combining two tests so that an individual both missed some drinks between meals and expressed fatigue was sensitive at 0.71 (95% CI 0.29 to 0.96) and specific at 0.92 (95% CI 0.83 to 0.97).There was sufficient evidence to suggest that several stand-alone tests often used to assess dehydration in older people (including fluid intake, urine specific gravity, urine colour, urine volume, heart rate, dry mouth, feeling thirsty and BIA assessment of intracellular water or extracellular water) are not useful, and should not be relied on individually as ways of assessing presence or absence of dehydration in older people.No tests were found consistently useful in diagnosing current water-loss dehydration. AUTHORS' CONCLUSIONS: There is limited evidence of the diagnostic utility of any individual clinical symptom, sign or test or combination of tests to indicate water-loss dehydration in older people. Individual tests should not be used in this population to indicate dehydration; they miss a high proportion of people with dehydration, and wrongly label those who are adequately hydrated.Promising tests identified by this review need to be further assessed, as do new methods in development. Combining several tests may improve diagnostic accuracy.

Fluid retention index predicts the 30-day mortality in geriatric care.

The incidence and medical consequences of dehydration and fluid retention in senior citizens are unclear. The present study used urine sampling to detect renal conservation of water, which is an early sign of dehydration, and assessed its relationship to mortality in elderly patients admitted for acute hospital care. A urine sample was collected from 256 patients (mean age 82 years) and analyzed for color, specific gravity and osmolality. These markers were used to calculate a composite index of fluid retention, which was indicated by urine color ≥ 4, specific gravity ≥ 1.020 and osmolality ≥ 600 mOsmol/kg as suggested from eight previous studies of exercise-induced dehydration, of which one extends to age 69. Concentrated urine consistent with dehydration was present in 39 (16%) of the patients. This finding was relatively more common among those with confusion and/or dementia, but less common in patients with medical disease, and in those taking diuretics daily. Patients with such fluid retention had a higher 30-day mortality when compared to those who were euhydrated (21% versus 8%; p < 0.03). A difference of 10% remained at three months and one year after the admission to hospital. Concentrated urine consistent with fluid retention was found in 16% of the geriatric patients admitted to hospital for acute care. In these patients the mortality within 30 days was almost tripled compared to those who were euhydrated.

Profiles of older patients in the emergency department: findings from the interRAI Multinational Emergency Department Study.

STUDY OBJECTIVE: We examine functional profiles and presence of geriatric syndromes among older patients attending 13 emergency departments (EDs) in 7 nations. METHODS: This was a prospective observational study of a convenience sample of patients, aged 75 years and older, recruited sequentially and mainly during normal working hours. Clinical observations were drawn from the interRAI Emergency Department Screener, with assessments performed by trained nurses. RESULTS: A sample of 2,282 patients (range 98 to 549 patients across nations) was recruited. Before becoming unwell, 46% were dependent on others in one or more aspects of personal activities of daily living. This proportion increased to 67% at presentation to the ED. In the ED, 26% exhibited evidence of cognitive impairment, and 49% could not walk without supervision. Recent falls were common (37%). Overall, at least 48% had a geriatric syndrome before becoming unwell, increasing to 78% at presentation to the ED. This pattern was consistent across nations. CONCLUSION: Functional problems and geriatric syndromes affect the majority of older patients attending the ED, which may have important implications for clinical protocols and design of EDs.

The use of a noninvasive hemoglobin monitor for volume kinetic analysis in an emergency room setting.

BACKGROUND: Distribution and clearance of an infused bolus can be studied by repetitive sampling of invasive total hemoglobin (tHb) using volume kinetic equations. Pulse CO-oximetry, a recent advancement in patient monitoring that allows for the continuous and noninvasive estimation of hemoglobin concentration (SpHb), would greatly facilitate the scientific and clinical use of the volume kinetic parameters. In the present study, we examined whether serial measurements of SpHb in an emergency room setting can be used to calculate distribution volume (V) and clearance (Cl) rate of an infused bolus. METHODS: This was a prospective, observational study of patients in 2 age groups admitted for various reasons to the emergency room of a tertiary care center. IV catheters were placed in both arms of the subjects to induce plasma volume expansion by infusion of a buffered crystalloid glucose solution and for withdrawing venous blood samples for analysis of tHb at 0, 5, 10, 15, 30, 45, 60, 75, and 90 minutes after start of infusion. During these interventions, subjects were simultaneously monitored by pulse CO-oximetry for measurement of SpHb (Masimo Radical-7, Rev E ReSposable Sensor). Bias, precision, and limits of agreement were calculated in Bland-Altman plots to compare the accuracy of SpHb with invasive tHb measurements. Using volume kinetic (pharmacokinetics for fluids) equations, V and Cl were determined. RESULTS: Thirty patients (14 from the young group with a mean age of 30 years, and 16 from the geriatric group with mean age of 84 years) were enrolled in the study. When all data were included, this yielded 242 data pairs with a bias of -0.47 (95% confidence interval, -0.62 to -0.32) between SpHb and tHb. However, 5 patients were omitted because of low quality signals, leaving 193 hemoglobin data pairs for further analysis. Bias was then -0.24 (95% confidence interval, -0.39 to -0.09). The biases show that the device on average slightly underestimates tHb values. The precision of SpHb decreases when the low signal quality indicator is present. For the 27 subjects for whom the V and Cl were calculated, there were no significant differences in the estimation of the distribution volumes using either tHb or SpHb values. Clearance constants were also estimated, but with less accuracy. CONCLUSIONS: Our data show that SpHb by pulse CO-oximetry may be used to calculate volume of distribution in an emergency room setting.

Diagnostic accuracy of calculated serum osmolarity to predict dehydration in older people: adding value to pathology laboratory reports.

OBJECTIVES: To assess which osmolarity equation best predicts directly measured serum/plasma osmolality and whether its use could add value to routine blood test results through screening for dehydration in older people. DESIGN: Diagnostic accuracy study. PARTICIPANTS: Older people (≥65 years) in 5 cohorts: Dietary Strategies for Healthy Ageing in Europe (NU-AGE, living in the community), Dehydration Recognition In our Elders (DRIE, living in residential care), Fortes (admitted to acute medical care), Sjöstrand (emergency room) or Pfortmueller cohorts (hospitalised with liver cirrhosis). REFERENCE STANDARD FOR HYDRATION STATUS: Directly measured serum/plasma osmolality: current dehydration (serum osmolality>300 mOsm/kg), impending/current dehydration (≥295 mOsm/kg). INDEX TESTS: 39 osmolarity equations calculated using serum indices from the same blood draw as directly measured osmolality. RESULTS: Across 5 cohorts 595 older people were included, of whom 19% were dehydrated (directly measured osmolality>300 mOsm/kg). Of 39 osmolarity equations, 5 showed reasonable agreement with directly measured osmolality and 3 had good predictive accuracy in subgroups with diabetes and poor renal function. Two equations were characterised by narrower limits of agreement, low levels of differential bias and good diagnostic accuracy in receiver operating characteristic plots (areas under the curve>0.8). The best equation was osmolarity=1.86×(Na++K+)+1.15×glucose+urea+14 (all measured in mmol/L). It appeared useful in people aged ≥65 years with and without diabetes, poor renal function, dehydration, in men and women, with a range of ages, health, cognitive and functional status. CONCLUSIONS: Some commonly used osmolarity equations work poorly, and should not be used. Given costs and prevalence of dehydration in older people we suggest use of the best formula by pathology laboratories using a cutpoint of 295 mOsm/L (sensitivity 85%, specificity 59%), to report dehydration risk opportunistically when serum glucose, urea and electrolytes are measured for other reasons in older adults. TRIAL REGISTRATION NUMBERS: DRIE: Research Register for Social Care, 122273; NU-AGE: ClinicalTrials.gov NCT01754012.

Volume kinetic analysis of fluid shifts accompanying intravenous infusions of glucose solution.

Volume kinetics is a mathematical tool for macroscopic (whole-body) evaluation of the distribution and elimination of fluid given by intravenous infusion. Although the kinetic system has mostly been applied to crystalloid fluids, such as Ringer's solution, it has more recently been extended to glucose solution, which is characterized by interdependence between glucose and fluid kinetics. The elimination of glucose, as estimated by a one-compartment open model, serves as the driving force for cellular uptake of glucose and, by virtue of osmosis, of water. Key findings include the observation that the infused fluid, besides being accumulated in the cells, occupies a central body fluid space (V1), which is no larger than 3-4 L, and that the cellular hydration has a much longer time-course than the hydration of V1. This explains the risk of hypovolemia associated with rapid infusion of 5% glucose; the dilution of V1, which is quite substantial owing to the small size of this space at baseline, stimulates a brisk diuresis while the excess water is being "trapped" in the cells along with the glucose. Model linearity has been demonstrated for 2.5% glucose solution and this allows the construction of nomograms for administration of such fluid during surgery and critical illness.

Lower dose of hypertonic saline dextran reduces the risk of lethal rebleeding in uncontrolled hemorrhage.

To challenge whether the recommended dose of 4 mL/kg of 7.5% sodium chloride in 6% Dextran (HSD) is optimal for fluid resuscitation in uncontrolled hemorrhage, 30 anesthetized pigs were randomized to receive a 5-min intravenous infusion of either 1, 2, or 4 mL/kg of HSD beginning 10 min after inducing a 5-mm laceration in the infrarenal aorta. In addition to conventional hemodynamic monitoring, the blood loss was calculated as the difference in blood flow rates between flow probes placed proximal and distal to the injury. The results show that the bleeding stopped between 3 and 4 min after the injury and amounted to 338+/-92 mL (mean +/- SEM), which corresponds to 28.5%+/-6.6% of the estimated blood volume. After treatment with HSD was started, six rebleeding events occurred in the 1-mL group, 11 in the 2-mL group, and 16 in the 4-mL group. The amount of blood lost due to rebleeding increased significantly with the dose of HSD and was also associated with a fatal outcome. The total blood loss was 408 mL in the survivors and 630 mL in the nonsurvivors (median, P < 0.007). The mortality in the three groups was 20%, 50%, and 50%, respectively. In conclusion, infusing 4 mL/kg of HSD after uncontrolled aortic hemorrhage promoted rebleeding and increased the mortality, while a dose of 1 mL/kg appeared to be more suitable.

Randomized controlled trial of a prehospital decision system by emergency medical services to ensure optimal treatment for older adults in Sweden.

OBJECTIVES: To evaluate the feasibility and appropriateness of a prehospital system allowing ambulance nurses to transport older adults directly to geriatric care at a community-based hospital (CH) or to an emergency department (ED). DESIGN: Randomized controlled trial. SETTING: Emergency medical services in Stockholm, Sweden. PARTICIPANTS: Older adults who called the emergency number were randomized to an intervention group (n = 410) or a control group (n = 396). INTERVENTION: The dispatcher randomized the individuals. Those randomized to the intervention group were transported to several alternative destinations decided by a trained nurse performing a comprehensive assessment, using the new prehospital system. Those randomized to the control group were transported to the ED. MEASUREMENTS: Primary endpoint: number of individuals triaged directly to a CH (feasibility). Secondary endpoint: number of subsequent transfers (appropriateness) from CH to ED within 24 hours after initial admission. RESULTS: After exclusion and crossover, the control group consisted of 217 and the intervention group of 449 older adults. The nurse sent 20% of the intervention group (90/449) (95% confidence interval (CI) = 16.6-24.0) directly to the CH when using the prehospital system. Six of those individuals (6.7%) (95% CI = 3.1-13.8) were subsequently transferred from the CH to the ED. Overall, the nurse appropriately triaged 93.3% of the participants (84/90) and transferred them to the CH, avoiding an ED visit. CONCLUSION: Ambulance nurses are able to send older adults to an alternative healthcare facility with the help of a prehospital decision support system. In this geographical setting, this appears to be a promising method to optimize resources and improve emergency care of elderly adults.

Geriatric syndromes predict postdischarge outcomes among older emergency department patients: findings from the interRAI Multinational Emergency Department Study.

OBJECTIVES: Identifying older emergency department (ED) patients with clinical features associated with adverse postdischarge outcomes may lead to improved clinical reasoning and better targeting for preventative interventions. Previous studies have used single-country samples to identify limited sets of determinants for a limited number of proxy outcomes. The objective of this study was to identify and compare geriatric syndromes that influence the probability of postdischarge outcomes among older ED patients from a multinational context. METHODS: A multinational prospective cohort study of ED patients aged 75 years or older was conducted. A total of 13 ED sites from Australia, Belgium, Canada, Germany, Iceland, India, and Sweden participated. Patients who were expected to die within 24 hours or did not speak the native language were excluded. Of the 2,475 patients approached for inclusion, 2,282 (92.2%) were enrolled. Patients were assessed at ED admission with the interRAI ED Contact Assessment, a geriatric ED assessment. Outcomes were examined for patients admitted to a hospital ward (62.9%, n=1,436) or discharged to a community setting (34.0%, n=775) after an ED visit. Overall, 3% of patients were lost to follow-up. Hospital length of stay (LOS) and discharge to higher level of care was recorded for patients admitted to a hospital ward. Any ED or hospital use within 28 days of discharge was recorded for patients discharged to a community setting. Unadjusted and adjusted odds ratios (ORs) were used to describe determinants using standard and multilevel logistic regression. RESULTS: A multi-country model including living alone (OR=1.78, p≤0.01), informal caregiver distress (OR=1.69, p=0.02), deficits in ambulation (OR=1.94, p≤0.01), poor self-report (OR = 1.84, p≤0.01), and traumatic injury (OR=2.18, p≤0.01) best described older patients at risk of longer hospital lengths of stay. A model including recent ED visits (OR=2.10, p≤0.01), baseline functional impairment (OR=1.68, p≤0.01), and anhedonia (OR=1.73, p≤0.01) best described older patients at risk of proximate repeat hospital use. A sufficiently accurate and generalizable model to describe the risk of discharge to higher levels of care among admitted patients was not achieved. CONCLUSIONS: Despite markedly different health care systems, the probability of long hospital lengths of stay and repeat hospital use among older ED patients is detectable at the multinational level with moderate accuracy. This study demonstrates the potential utility of incorporating common geriatric clinical features in routine clinical examination and disposition planning for older patients in EDs.

Elderly patients' participation in emergency medical services when offered an alternative care pathway.

As organizational changes in the healthcare system are in progress, to enhance care quality and reduce costs, it is important to investigate how these changes affect elderly patients' experiences and their rights to participate in the choice of healthcare. The aim of this study is to describe elderly patients' lived experience of participating in the choice of healthcare when being offered an alternative care pathway by the emergency medical services, when the individual patient's medical needs made this choice possible. This study was carried out from the perspective of caring science, and a phenomenological approach was applied, where data were analysed for meaning. Data consist of 11 semi-structured interviews with elderly patients who chose a healthcare pathway to a community-based hospital when they were offered an alternative level of healthcare. The findings show that the essence of the phenomenon is described as "There was a ray of hope about a caring encounter and about being treated like a unique human being". Five meaningful constituents emerged in the descriptions: endurable waiting, speedy transference, a concerned encounter, trust in competence, and a choice based on memories of suffering from care. The conclusion is that patient participation in the choice of a healthcare alternative instead of the emergency department is an opportunity of avoiding suffering from care and being objectified.

Developing a decision support system for geriatric patients in prehospital care.

OBJECTIVES: To develop a feasible and safe prehospital decision support system (DSS) for the emergency medical services (EMS), facilitating safe steering of geriatric patients to an optimal level of healthcare. METHODS: The development process involves four consecutive steps. The first step was gathering data from patients transported by EMS, with the electronic patient care record, to retrospectively identify appropriate patient categories for steering. The second step was to allow a group of medical experts to give advice and suggestions for further development of the DSS. The third step was validation of the decision support tool and the fourth step was validation of the entire prehospital DSS in a pilot study. RESULTS: The patient categories relevant to steering were those medical conditions that the geriatric clinicians felt confident in receiving from the EMS. A prehospital DSS was then developed for these 11 medical conditions. The evaluation and validation of the DSS showed a high degree of compliance with the patients' final level of healthcare. The pilot study included 110 randomized patients; 33.9% were triaged to an alternative level of healthcare, that is geriatric care or primary care. No medical inaccuracies or secondary transports from alternative care to the hospital emergency department were identified. CONCLUSION: Using this prehospital DSS - developed for 11 medical conditions - the Swedish prehospital nurse can safely decide on the level of healthcare to which an elderly patient can be steered.

Differentiating frailty in older people using the Swedish ambulance service: a retrospective audit.

The elderly population in Sweden is increasing. This will lead to an increased need for healthcare resources and put extra demands on healthcare professionals. Consequently, ambulance personnel will be faced with the challenge of meeting extra demands from increasing numbers of older people with complex and atypical clinical presentations. Therefore we highlight that great problems exist for ambulance personnel to understand and meet these patients' care needs. Using a caring science approach, we apply the patient's perspective, and the aim of this study is to identify and illuminate the conditions that affect elderly people assessed with the assessment category "general affected health condition". Thus, we have analyzed the characteristics belonging to this specific condition. The method is a retrospective audit, involving a qualitative content analysis of a total of 88 emergency service records. The conclusion is that by using caring science, the concept of frailty which is based on a comprehensive understanding of human life can clarify the state of "general affected health condition", as either illness or ill-health. This offers a new assessment category and outlines care and treatment that strengthen and support the health and wellbeing of the individual elderly person. Furthermore, the concept of frailty ought to be included in "The International Statistical Classification of Diseases and Related Health Problems" (ICD-10).

Thirst in the elderly with and without heart failure.

Elderly patients with heart failure (HF) may be troubled by thirst, despite the fact that elderly have an impaired ability to sense thirst. The present study was undertaken to compare the intensity of thirst in patients with and without HF and to evaluate how this symptom relates to the health-related quality of life and indices of the fluid balance. Forty-eight patients (mean age 80 years) admitted to hospital with worsening HF (n = 23) or with other acute illness (n = 25) graded their thirst and estimated their health-related quality of life (HRQoL). Serum sodium was measured and urine samples were assessed for color and electrolyte content. The HF patients reported significantly more intensive thirst (median = 75 mm) compared with those in the control group (median = 25 mm; p < 0.0001). There was no statistically significant relationship between thirst and HRQoL, which was low overall. Serum sodium and urine color did not differ significantly between the groups, but the urine of the HF patients had a lower sodium concentration and osmolality. We conclude that elderly patients with worsening HF have considerably increased thirst and, hence, intense thirst should be regarded as a symptom of HF.

Modelling of peripheral fluid accumulation after a crystalloid bolus in female volunteers - a mathematical study.

OBJECTIVE: To simultaneously model plasma dilution and urinary output in female volunteers. METHODS: Ten healthy female non-pregnant volunteers, aged 21-39 years (mean 29), with a bodyweight of 58-67 kg (mean 62.5 kg) participated. No oral fluid or food was allowed between midnight and completion of the experiment. The protocol included an infusion of acetated Ringer's solution, 25 ml/kg over 30 min. Blood samples (4 ml) were taken every 5 min during the first 120 min, and thereafter the sampling rate was every 10 min until the end of the experiment at 240 min. A standard bladder catheter connected to a drip counter to monitor urine excretion continuously was used. The data were analysed by empirical calculations as well as by a mathematical model. RESULTS: Maximum urinary output rate was found to be 19 (13-31) ml/min. The subjects were likely to accumulate three times as much of the infused fluid peripherally as centrally; 1/µ = 2.7 (2.0-5.7). Elimination efficacy, E(eff), was 24 (5-35), and the basal elimination k(b) was 1.11 (0.28-2.90). The total time delay T(tot) of urinary output was estimated as 17 (11-31) min. CONCLUSION: The experimental results showed a large variability in spite of a homogenous volunteer group. It was possible to compute the infusion amount, plasma dilution and simultaneous urinary output for each consecutive time point and thereby the empirical peripheral fluid accumulation. The variability between individuals may be explained by differences in tissue and hormonal responses to fluid boluses, which needs to be further explored.

Intravenous hydration with a 2.5% glucose solution in Type II diabetes.

Physicians are often unclear about how fast intravenous glucose solutions should be administered to adequately hydrate patients with Type II diabetes while avoiding hyperglycaemia and excessive plasma volume expansion. The aim of the present study was to analyse the disposition of a 2.5% glucose solution and create a nomogram which could serve as a guide to fluid therapy in these patients. Twelve males (mean body mass index, 29 kg/m(2)) with Type II diabetes due to insulin resistance, as quantified by an euglycaemic hyperinsulinaemic glucose clamp, received an infusion of iso-osmotic 2.5% glucose solution with electrolytes (70 mmol/l sodium, 45 mmol/l chloride and 25 mmol/l acetate) at individual rates over 30 and 60 min respectively. Blood glucose and haemoglobin levels were measured repeatedly over 3.5 h to estimate the kinetics of glucose and fluid volume. Mean insulin sensitivity was 4.2x10(-4) dlxkg(-1)xmin(-1)x(micro-units/ml)(-1). The individualized infusion rates reached the predetermined blood glucose level of 12 mmol/l with a mean difference of 0.2 mmol/l. The disposition of glucose was an important factor governing fluid distribution. The volume of distribution of exogenous glucose averaged 19.8 litres, but for the fluid volume it was only 3.7 litres. The clearance was 0.37 litre/min for glucose and 0.10 litre/min for the fluid volume, and the results of the 30-min and 60-min infusions agreed reasonably well. It is concluded that kinetic analysis can be used to guide the infusion time and infusion rate of 2.5% glucose to reach any predetermined glucose level and volume expansion.

Tranexamic acid does not prevent rebleeding in an uncontrolled hemorrhage porcine model.

BACKGROUND: Fluid resuscitation after uncontrolled hemorrhage might promote rebleeding and irreversible shock. Tranexamic acid is a procoagulant drug that limits blood loss after surgery of the hip, knee, and heart. We hypothesized that pretreatment with tranexamic acid reduces the rebleeding in uncontrolled hemorrhage and thereby allows safe administration of crystalloid fluid resuscitation. METHODS: A 120-minute intravenous infusion of 100 mL/kg of Ringer's solution was given to 24 pigs (mean weight, 20 kg) 10 minutes after lacerating the infrarenal aorta. The animals were randomized to receive an intravenous injection of 15 mg/kg of tranexamic acid or placebo just before starting the resuscitation. Rebleeding events were monitored by two ultrasonic probes positioned proximal and distal to the laceration. RESULTS: Tranexamic acid had no effect on the number of rebleeding events, bled volume, or mortality. The initial bleeding stopped within 4 minutes after the injury. The five animals that died suffered from 4.4 rebleeding events on average, which tripled the total blood loss, whereas the survivors had only 1.3 such events during fluid resuscitation (p < 0.02). At autopsy, death was associated with a larger total hemorrhage; the blood recovered from the abdomen weighed 1.4 kg (median) in nonsurvivors and 0.6 kg in survivors (p < 0.001), with the difference being attributable to rebleeding. CONCLUSION: Rebleeding events increased the amount of blood lost and the mortality in uncontrolled aortic hemorrhage. Tranexamic acid offered no benefit.