Receiving Maintenance Fluids Research Articles

Association between dextrose-containing maintenance fluids and phosphorus supplementation during total parenteral nutrition initiation in adult patients who were hospitalized: A retrospective cohort study.

Use of dextrose-containing maintenance fluids prior to parenteral nutrition (PN) initiation is speculated to reduce the risk for refeeding syndrome. We aimed to assess if the use of dextrose vs nondextrose maintenance fluids before PN initiation changes electrolyte supplementation requirements and shifts during initiation. This retrospective cohort study included patients who received nothing by mouth but received maintenance fluids ≥72 h before PN. The major end point was phosphorus supplementation over 48 h following nutrition initiation. Minor end point included other electrolyte supplementation, changes in electrolyte levels, time to discharge, and goal kilocalories per day. Fifty-three patients between August 1, 2019, and August 26, 2020, met criteria for analysis; 60% (n = 32) used a dextrose and 40% (n = 21) used a nondextrose maintenance fluid. Baseline characteristics were similar between fluid groups except for body mass index (25.1 dextrose vs 27.5 kg/m2 nondextrose), sex (43.8% female vs 52.4% male), and severe malnutrition (46.9% vs 28.6%), respectively. Phosphorus (52.5 vs 50 mmol; P = 0.33) and magnesium (24 vs 22 g; P = 0.63) supplementation 48 h following nutrition initiation were similar between groups; however, potassium supplementation was lower in the dextrose group (165.0 vs 208.7 mEq; P = 0.01). No difference was observed between groups for time to discharge following nutrition initiation or time to goal kilocalories per day. After controlling for patients who were malnourished between fluid groups using linear regression, phosphorus repletion differences remained nonsignificant. This study did not detect a difference in phosphorus supplementation between groups, even after controlling for patients who were malnourished.

Association Between Hyponatremia and Maintenance Intravenous Solutions in Critically Ill Children: A Retrospective Observational Study.

Objetive: We sought to determine the association between maintenance intravenous solutions and the presence of hyponatremia in children in pediatric intensive care (PICU).Materials and Methods: An analytical observational study in children hospitalized in the PICU between January 2015 and December 2018. Patients who received maintenance fluids within the first 48 h after admission and who had at least two serum sodium levels drawn during this time were included.Measurements and Main Results: A total of 1,668 patients were admitted to the PICU during the study period, 503 of whom met the inclusion criteria. The median age was 24 months (IQR 8–96) and 50.9% were female. Altogether, 24.1% of the children developed hyponatremia; it was more frequent in those who received hypotonic solutions (63 vs. 37%; OR 1.41 95% CI 0.92, 2.15 p = 0.106), who also had a longer hospital stay (20 vs. 14 days, difference in means 8 days, 95% CI 2.67, 13.3, p = 0.001). Children who received loop diuretics and those who were post-operative had a greater risk of developing hyponatremia if they received hypotonic solutions (aOR 2.1 95% CI 1.41, 3.0, p = 0.000). Those with balanced isotonic solutions had a lower risk of developing hyponatremia (aOR 0.59 95% CI 0.35, 0.99, p = 0.004) and hyperchloremia (aOR 0.51 95% CI 0.34, 0.77, p = 0.000), adjusted for disease severity. A greater risk of death was found in the group with severe hyponatremia <130 mEq/L (aOR 9.75 95% CI 1.64–58.15; p = 0.01).Conclusions: Hyponatremia associated with the use of hypotonic maintenance solutions occurs in one out of four children in intensive care. The use of these solutions is associated with a longer hospital stay, and the main risk groups are post-operative patients and those who receive loop diuretics. Clinical studies are needed to determine which maintenance solutions have the greatest efficacy and safety in critically ill children.

DO WE STILL “TREAT” CHILDREN WITH HYPOTONIC INTRAVENOUS FLUIDS?

Aim The National Patient Safety Agency (NPSA) alert, “Reducing the risk of hyponatraemia when administering intravenous infusions to children,” gives clear guidance on fluid management1. The following study reviewed intravenous fluid management in children to identify: ▸ Which fluids are given to children ▸ If hospitals had removed sodium chloride 0.18% in glucose 4% from stock ▸ The extent of hyponatraemia ▸ If hospitals have clinical guidelines for fluid management in children. Method A national multi-sectional study was conducted for paediatric patients (both medical and surgical), providing they met the inclusion criteria: ▸ aged 0–18 years and ▸ receiving intravenous fluids or fluids had been stopped in previous 24 hours. Children receiving intensive care were excluded. A data collection tool was completed by pharmacists for one to four days in each hospital, noting age, weight, clinical background, indication, fluids administered, including rate and electrolyte monitoring. Respondents were asked for their local clinical guideline for fluid management in children. Results 216 patients were recruited from 28 hospitals. 200 children received maintenance fluids and 44 received replacement fluid for volume expansion. Hypotonic maintenance fluids (sodium chloride Hyponatraemia was noted in 20 patients (nine received hypotonic solutions, nine isotonic and two patients hypertonic fluids). Forty-seven patients (22%) had no electrolyte monitoring following fluid initiation. Forty-one patients received greater than 100% of the maintenance volume calculated using the Holliday and Segar calculation.2 Of these two patients experienced hyponatraemia. Twenty-five hospitals (89%) had intravenous fluid guidelines in place. This represents a 60% increase in guideline availability since the evaluation conducted by Armon et al in 2004, before the NPSA publication.3 Conclusion Practice following the NPSA publication is changing. No child received 0.18% sodium chloride in 4% glucose. Most children receive volume expansion with an isotonic solution but maintenance fluids still tend to be hypotonic. Most, but not all hospitals, have intravenous fluid guidelines in place for children. Despite changes in practice, we have not yet found the perfect intravenous fluid (20 patients had hyponatraemia), hence further changes are necessary. There is now a licensed isotonic solution available which is used at the author9s institution. More care needs to be taken with regard to regular electrolyte monitoring and the volume of fluid administered.

Isotonic intravenous maintenance fluid reduces hospital acquired hyponatremia in young children with central nervous system infections.

To find the appropriate type of intravenous fluid (isotonic vs. hypotonic saline in 5 % dextrose) for empiric maintenance fluid therapy in children with central nervous system (CNS) infections that reduces the incidence of hospital acquired hyponatremia. This blinded randomized controlled trial included hospitalized children aged 3 mo to 5 y with suspected CNS infections requiring intravenous maintenance fluid for at least 24 h. The subjects were randomized to receive 0.9 % saline (Group-A), 0.45 % saline (Group-B) and 0.18 % saline (Group-C) at standard maintenance rate. The outcome measures were proportion of patients developing hyponatremia (serum sodium < 135 mmol/L) after 24 h and serum sodium values at 6, 12, 18, 24 h of receiving maintenance fluids. Of the 92 patients enrolled, 31, 30 and 31 patients were randomized to Group A, B and C, respectively. Majority (60.7 %) of the patients in Group-C developed hyponatremia compared with 7.1 % of the children in Group-A and 46.1 % in Group-B. During first 24 h of fluid administration successive fall in the serum sodium values was observed in patients receiving hypotonic fluids. The risk of developing hyponatremia was nearly 6½ (95 % confidence interval (CI) 1.6-26) to 8.5 (95 % CI 2.16-33.39) times more in patients who received hypotonic saline compared to those who received isotonic saline. Administration of 0.9 % saline in 5 % dextrose as intravenous maintenance fluid in children with CNS infection leads to significantly less incidence of hyponatremia when compared to that with hypotonic fluids.

Transfer of evidence‐based medical guidelines to low‐ and middle‐income countries

keywords evidence-based medicine, guidelines, tropical medicine, low- and middle-income countriesEvidence-based medicine is widely accepted to guidemedical recommendations: clinical or diagnostic guidelinesare developed on the grounds of the best available data,systematic reviews and sound clinical understanding(Sackett et al. 1996). But occasionally the quality of theevidence may not be as good as expected (Kett et al. 2011).In the absence of high-quality data, one has to rely oninformation generated through studies with suboptimaldesigns and based on mere empirical – frequentlysubjective – experience. Important medical problemsoccurring in high-income countries can, depending on site-specific conditions, provoke much more severe challengeswhen occurring in low- and middle-income countries(LMICs).Most clinical guidelines not directly related to tropicalmedicine cannot or do not consider trials performed inLMICs, because, for many medical conditions, such trialshave either not been conducted there or are of questionablequality. Technical prerequisites, ethical issues, infrastruc-tural constraints, overburdened health systems and, fre-quently, the lack of appropriate funding prevent successfuland meaningful realization of clinical trials in LMICs. As aresult, conclusions on the applicability of guidelines thathave proven valuable in high-income countries are difficultto draw for LMICs.The clinical guideline for haemodynamic support ofpaediatric and neonatal septic shock proposed by theAmerican College of Critical Care Medicine (Brierley et al.2009), for example, suggests early fluid administration as aprimary therapeutic measure. And, if applicable, thismeasure should be taken in conjunction with intercon-nected measures such as inotropic support, close haemo-dynamic monitoring and mechanical ventilation. Thisguideline and the algorithm proposed are largely acceptedin high-income countries.Severefebrileconditions causingasystemicinflammatoryresponse syndrome are important causes of morbidity andmortality in LMICs. This applies particularly to childrenand fevers with underlying causes such as malaria andsepticaemia. In LMICs, diagnostic resources and accurateclinical monitoring, including treatment options, are oftenlimited. Recently a multicentre, open, randomized con-trolledtrial onfluidmanagementinKenyan,TanzanianandUgandan children was designed to apply fluid boluses assuggested by the aforementioned guideline (Maitland et al.2011). The children were suffering from severe febrileillnesses complicated by impaired consciousness and/orrespiratory distress and showed evidence of impairedperfusion. Upon admission to hospital, they were treatedwith boluses of either albumin or saline. In addition, thechildren received maintenance fluids and, in cases ofhaemoglobin levels below 5 g/dl, whole blood transfusionsof 20 ml/kg over a period of 4 h. Bolus volumes wereincreased after a protocol amendment. The result of thestudy was that fluid boluses significantly raised the 48-hmortality, andas a consequence, the trial had to bestopped.The study was performed in ‘typical African hospitals,which have no intensive care facilities’ (Maitland et al.2011). Although complications due to fluid overload werereported to be rare, the outcome of the study and its haltingahead of schedule recommended by the Data and SafetyMonitoring Committee indicate that potential complica-tions were not perceived in due time, most likely due to thelack of diagnostic means and merely clinical assessments.The investigators singled out and evaluated one specificintervention from the set of complex and interconnectedprocedures outlined in the guideline. This important studyraises the fundamental question about the applicability ofguidelines in LMICs when data were generated in high-income settings and vice versa, in addition to a number ofweighty arguments put forward by others (Southall &Samuels 2011).Chinnock et al. (2005) have emphasized that ‘the rele-vance of systematic reviews to frontline health care

Fluid Boluses Possibly Harmful in Some Settings

Source: Maitland K, Kiguli S, Poka RO, et al. Mortality after fluid bolus in African children with severe infection. N Engl J Med. Epub 2011 May 26; doi: 10.1056/NEJMoa1101549The Fluid Expansion as Supportive Therapy (FEAST) group of investigators from Africa and the United Kingdom evaluated the effects of rapid infusion normal saline or albumin compared with intravenous maintenance fluids in children with a severe febrile illness and impaired consciousness and/or respiratory distress accompanied by impaired perfusion. This clinical trial in Uganda, Kenya, and Tanzania enrolled more than 3,000 children aged 60 days to 12 years from January 2009 to January 2011. Stratum A included children without severe hypotension who had one or more of: capillary refill at least three seconds; lower extremity temperature gradient; weak radial pulse; or severe tachycardia. Stratum B included children with impaired perfusions and severe hypotension. Children with severe malnutrition, gastroenteritis, or noninfectious causes of shock were excluded. Stratum A children were randomized to receive 20 ml/kg normal saline, 20 ml/kg albumin, or no boluses (controls). Stratum B children were randomized to receive either normal saline or albumin bolus. Children received intravenous maintenance fluids, antibiotics, antimalarials, anticonvulsants, treatment for hypoglycemia, and transfusions for hemoglobin less than 5 g/dL. The primary end point was mortality at 48 hours. Secondary end points included hypotensive shock within 48 hours, neurologic sequelae at 4 or 24 weeks, and mortality at 4 weeks.Stratum A randomized 3,141 and Stratum B randomized 29 children. Baseline characteristics for all groups were similar: median age 24 months; 62% with prostration; 15% comatose; 83% in respiratory distress; 51% with moderate to severe acidosis; malaria in 57%; and 4% positive for HIV. Children in the two treatment arms received four times more fluid than did control children (40 ml/kg vs 10 ml/kg). Stratum A mortality within the first 48 hours was 10.5% receiving saline bolus, 10.6% receiving albumin, and 7.3% receiving maintenance fluids, with a relative risk of death of 1.45 for any bolus as compared to controls (95% CI, 1.13–1.86; P=.003). Mortality at four weeks was 12.0%, 12.2%, and 8.7% in the three groups, respectively (P=.004 for bolus vs control). Stratum B mortality was 56% in the saline group and 69% in the albumin group (P=.17). Prior to achieving the enrollment goal of 3,600, the study was stopped due to higher mortality among children receiving bolus fluids.The investigators conclude that fluid boluses significantly increased 48-hour mortality in critically ill children with impaired perfusion in these resource-limited settings.Drs Berg and Bratton have disclosed no financial relationship relevant to this commentary. This commentary does not contain a discussion of an unapproved/investigative use of a commercial product/device.This study calls into question the rapid administration of a fluid bolus as an important determinant of positive resuscitation outcome. 1 In resource-limited areas where intensive care facilities are lacking, WHO guidelines reserve fluid resuscitation for advanced shock. Hence, most children in sub-Saharan Africa receive no more than maintenance fluids along with blood transfusions for severe anemia.2There are unique factors in the study population and setting that deserve consideration before application to a wider population, including limited equipment, monitoring capability, and treatments as compared to a modern critical care unit. The value of the intensive care unit environment should not be underestimated.3 It allows the careful titration of fluid, vasopressors to optimize hemodynamics, and mechanical ventilation for pulmonary edema and respiratory failure. Fluid bolus administration in this study was done over one hour, much slower than recommended for sepsis in the critical care literature (up to 60 ml/kg in 15 minutes). Only 7% to 9% of subjects were dehydrated, an unusual finding in pediatric shock patients in resource-rich areas.One important potential confounder can be found in the Supplement Appendix Table 3a accompanying this article (nejmoa1101549_appendix.pdf). In the first hour, 20% of the no-bolus group received a blood transfusion, versus 4% in the saline and 2% in the albumin group. This may have skewed the results to show the beneficial effect of a blood transfusion in the control group, rather than a negative effect of bolus fluids in the intervention groups. The harmful effect of a saline bolus versus no-bolus was statistically significant in patients with a hemoglobin less than 5 gm/dL but not in those with a higher hemoglobin. Could this be because the severely anemic patients needed blood, not a fluid bolus? The conclusions, while perhaps applicable to patients in sub-Saharan Africa, should not be applied to wider populations or locations without further investigation. The results of a single study performed in a unique environment do not disprove the beneficial effects of bolus fluid resuscitation on mortality4 and hospital length of stay when advanced critical care resources are available.5,6

Loss of complexity characterizes the heart rate response to experimental hemorrhagic shock in swine*

To improve our ability to identify physiologic deterioration caused by critical illness, we applied nonlinear and frequency-domain analytical methods to R-to-R interval (RRI) and systolic arterial pressure (SAP) time series during hemorrhagic shock. Prospective, randomized, controlled trial. Animal laboratory of a government research institute. Twenty swine (weight 36.4+/-0.11 kg). Fixed-volume hemorrhage followed by resuscitation; off-line analysis of RRI and SAP data. Anesthetized swine (shock group, n=12) underwent withdrawal of 30 mL/kg blood in 10 mL/kg decrements. A control group (n=8) received maintenance fluids only. Electrocardiogram and arterial pressure waveforms were acquired at 500 Hz. Eight hundred-beat data sets were analyzed at six time points: at baseline, after each blood withdrawal, after lactated Ringer's resuscitation, and after infusion of shed blood. Nonlinear methods were used to estimate the complexity (approximate entropy, sample entropy, Lempel-Ziv entropy, normalized entropy of symbol dynamics), RRI bits per word, and fractal dimension by curve lengths and by dispersion analysis of the RRI and SAP time series. Fast Fourier transformation was used to measure the high-frequency and low-frequency powers of RRI and SAP. Baroreflex sensitivity was assessed in the time domain with the sequence method. Hemorrhagic shock caused decreases in RRI complexity as quantified by approximate entropy, sample entropy, and symbol dynamics; these changes were reversed by resuscitation. Similar but statistically insignificant changes in fractal dimension by curve lengths were seen. RRI high-frequency power decreased with hemorrhagic shock-indicating withdrawal of vagal cardiac input-and was restored by resuscitation. Similar changes in baroreflex sensitivity were seen. Hemorrhagic shock did not affect SAP complexity. Hemorrhagic shock caused a reversible decrease in RRI complexity; these changes may be mediated by changes in vagal cardiac control. Assessment of RRI complexity may permit identification of casualties with hemorrhagic shock.

Comparison of Albumin and Saline for Fluid Resuscitation in the Intensive Care Unit

Intervention: Patients were randomly assigned to receive either 4% albumin or normal saline, with randomization stratified according to institution and whether there was a diagnosis of trauma on admission to the ICU. Study fluids were supplied in identical 500-ml bottles, and blinding was ensured through the use of specially designed masking cartons and specially designed and manufactured administration sets. The effectiveness of the blinding was confirmed in a formal study before the trial was initiated. The treating clinicians determined the amount and rate of fluid administration. In addition to the study fluid, patients received maintenance fluids, specific replacement fluids, enteral or parenteral nutrition, and blood products at the discretion of the treating clinicians. The monitoring of central venous pressure, pulmonary-artery catheterization, and all other aspects of patient care were performed at the discretion of the treating clinicians.

O.45 Effects of growth hormone and insulin-likegrowth factor 1 on PMN phagocytosis and monocyte HLA-DR expression in postoperative patients

blanace between secretion from the liver and degradation mainly in the kidney. Effects of severe trauma on plasma GSH levels are not known. Aim: To measure the altered plasma levels of GSH due to severe injury and their changes due to TPN with or without rhGH in trauma victims. Methods: Plasma levels of total GSH (pM, enzymatic recycling procedure) in 14 post-absorptive normals and 24 severely injured (ISS = 31 _+ 2), hypermetabolic (REE = 1.28 + 0.04 BEE) and hypercataboiic patients once within 48-60 hrs after injury when they were receiving maintenance fluids with no calorie or N and again after 3 and 7 days of TPN with (n = 12, Group H) or without (n = 12, Group C) rhGH (0.15 mg/kg/d). Results: GSH plasma levels in trauma patients (1.52 _+ 0.18 pM) under basal conditions (day 0) are not significantly different from uninjured normals (1.67 _+ 0.17pM), showing that severe injury has little or no effect on plasma GSH levels. The time course of the changes in plasma GSH in trauma victims are (mean _+ SEM, pM):

Reprioritization of liver protein synthesis resulting from recombinant human growth hormone supplementation in parenterally fed trauma patients: the effect of growth hormone on the acute-phase response.

One of the major components of the metabolic response to severe trauma is the alteration in concentrations of a large number of plasma proteins referred to as acute-phase proteins (APP). The principle mediators of these liver-synthesized APP are mainly the cytokines interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-alpha). We have measured the plasma levels of IL-6, TNF alpha, and 20 APP in 24 adult, severely injured, hypermetabolic and highly catabolic patients with multiple injuries within 48-60 hours after injury, when they were receiving maintenance fluids without calories or nitrogen, and subsequently during 7 days of total parenteral nutrition with (n = 12) or without (n = 12) recombinant human growth hormone supplementation (rhGH, 0.15 mg/kg/d). Baseline positive APP due to severe trauma include C-reactive protein (CRP), alpha-1 antichymotrypsin, alpha-1 acid glycoprotein, alpha-1 antitrypsin, fibronectin, and factor B. Negative APP include IgG, IgM, complement-3, prealbumin, transferrin, ceruloplasmin, and albumin. Except for CRP, alpha-1 antichymotrypsin, and albumin, all the APP levels increase during 7 days of nutritional support. Plasma levels of cytokines IL-6 and TNF-alpha, although initially markedly increased after injury, decrease with parenteral refeeding. There is a linear correlation between CRP and IL-6 levels and also between the transport proteins prealbumin and transferrin. Trauma-induced increases in CRP and IL-6 levels decreased with nutrition alone, but did not change with rhGH supplementation. An immunosuppressed state of injury is evident from the decreased immunoglobulin levels (IgG, IgM, IgA) in the trauma patients. Total parenteral nutrition alone increases the immunoglobulin levels to normal. However, with adjuvant rhGH, only IgA levels are normalized. Adjuvant rhGH therapy does not attenuate the reprioritization of acute liver protein synthesis and results in only limited restoration of host defenses. The clinical implications of these findings await further study.

Nitroglycerin attenuates the bowel damage of necrotizing enterocolitis in a rabbit model

Endogenous enteric nitric oxide has multiple functions. Enteric nitric oxide may be diminished in the premature infant and may therefore predispose the immature intestine to injury. The aim of this study was to determine if the infusion of a nitric oxide donor (nitroglycerin) would attenuate intestinal damage in a rabbit model of necrotizing enterocolitis. Transmural injection of rabbit intestinal loops with an acidified solution of casein and calcium gluconate simulates certain aspects of necrotizing enterocolitis. After injection of acidified casein solution into rabbit intestinal loops, twelve rabbits were randomly divided into two groups: six received maintenance fluids only and six received maintenance fluids and a nitroglycerin infusion adjusted to maintain mean arterial pressure 10 mm Hg below baseline (range, 2 to 12 μg/kg/min). After 3 hours, the rabbits were killed, and the intestinal tissue graded histologically. Intestinal damage in the nitroglycerin-treated rabbits was significantly less than that of untreated controls (mean histological grade of 0.39 v 1.48, P < .001). In this rabbit model of necrotizing enterocolitis, infusion of the nitric oxide donor nitroglycerin significantly attenuates intestinal damage. We speculate that enteric nitric oxide deficiency, as may exist in the preterm infant, predisposes the intestine to necrotizing enterocolitis.

Maintaining normal intracranial pressure in a rabbit model during treatment of severe diabetic ketoacidemia.

Increased intracranial pressure (ICP) resulting in death or neurologic morbidity continues to complicate traditional management of diabetic ketoacidemia (DKA) in pediatric patients. When ICP or cerebrospinal fluid pressures have been measured, correction of hyperglycemia in animals and treatment of DKA in humans have consistently resulted in pathologic increases in ICP. We hypothesized that elevations in ICP can be minimized if changes in effective osmolality (Eosm) are controlled during treatment of DKA. During a six-hour study period, three groups of rabbits were studied: a normal control group of nondiabetic animals (Cnor, n = 10), a control group of animals with DKA (CDKA, n = 8), and an experimental group of animals with DKA (EDKA, n = 8). There was no significant difference between the two groups with DKA regarding pretreatment degree of dehydration, blood pressure, hyperglycemia, acidemia or ICP. During the treatment period, Cnor received maintenance fluids only. CDKA received insulin and an assumed volume of deficit (150 ml/kg) along with maintenance fluids and urinary output replacement with 0.45% NaCl. EDKA received insulin and one-half the volume of deficit calculated by the weight lost with 0.9% NaCl plus maintenance fluids. There was no significant difference between CDKA and EDKA regarding the rate at which DKA was corrected. While CDKA demonstrated a progressive and statistically significant increase in ICP, EDKA exhibited no such increase in ICP compared to normal, nondiabetic controls (Cnor) during treatment. Changes in Eosm during treatment in CDKA compared to Cnor and in CDKA compared to EDKA were significantly greater (p < .01), however, changes in EOSM in EDKA compared to Cnor were not significant. These data support the clinical observation that decreasing EOSM during treatment of DKA is associated with increased ICP and suggest that DKA can be treated effectively with i.v. fluids and insulin without increasing ICP.

Plasma levels of insulin-like growth factor binding protein-3 in acute trauma patients

Insulin-like growth factors (IGFs) are a family of polypeptides that regulate cell growth. Their action and bioavailability are modified by binding proteins such as IGF binding protein-3 (IGFBP-3). Plasma IGFBP-3 level was found to be growth hormone (GH)-dependent, which makes detection of IGFBP-3 useful in the evaluation of GH secretion. In the early catabolic flow phase of severe injury, when plasma levels of GH and IGF-1 are low versus uninjured levels, the role of IGFBP-3 has not been investigated. We have measured basal levels of these polypeptide hormones in 16 adult (13 men and three women aged 47 ± 7 years) severely injured (Injury Severity Score, 32 ± 2), hypermetabolic resting energy expenditure [REE] to basal energy expenditure [BEE] ratio, 1.30 ± 0.05), ventilator-dependent, multiple-trauma patients within 48 to 60 hours of injury when the patients were receiving maintenance fluids without calories or nitrogen. These basal values were compared with those of 16 age-matched postabsorptive normals. In the catabolic flow phase of injury, plasma levels of GH, IGF-1, and IGFBP-3 were significantly reduced by 50%, 46%, and 45%, respectively. There was a significant linear inverse relationship between IGFBP-3 and age and also a positive correlation between IGFBP-3 and IGF-1 in both control and injured subjects. The ratio of IGFBP-3 to IGF-1 was not changed in trauma victims. Measurement of plasma IGFBP-3 levels has potential as a marker for monitoring GH therapeutic efficacy.

Pulsatile nature of growth hormone levels in critically ill trauma victims.

Circulating growth hormone (GH) levels in normal persons fluctuate widely because of pulsatile GH secretion. It is not known whether this pulsatile nature and rhythmicity exist in severe injury. These data become necessary to decide the timing of supplementary GH administration for its optimal utilization. The purpose of this study was to investigate the GH circadian variation with respect to that of insulin-like growth factor-1 (IGF-1), insulin, C-peptide, and cortisol in the early flow phase of injury. Plasma GH, IGF-1, insulin, C-peptide, and cortisol levels were measured at 1-hour intervals during 24 hours (8 AM to 8 AM) in 10 severely injured adults with multiple trauma during the early catabolic flow phase 24 to 48 hours after injury, when patients received maintenance fluids without calories or nitrogen. The 24-hour integrated GH concentration is not different from either 12-hour mean diurnal or 12-hour mean nocturnal or mean 8 AM GH concentration. Pulsatile GH bursts persist in injured patients during both day and night. Pulsatile bursts do not exist for IGF-1, insulin, and C-peptide. The plasma levels of cortisol show time-dependent daily maximum and minimum levels. Pulsatile GH bursts persist in injured patients but less frequently than seen in normal persons. The time of bolus administration of GH to augment the anabolic GH action in patients with trauma does not matter; however, for convenience morning administration may be preferable for patients in the intensive care unit.

Protein and glucose fuel kinetics and hormonal changes in elderly trauma patients

We investigated the responsiveness of whole-body protein and glucose kinetics to severe trauma and the role of regulatory hormones in the early catabolic “flow phase” of injury in a group of patients ranging in age from 19 to 85. Energy metabolism (indirect calorimetry), protein kinetics (primed-constant infusion of [ 15N]glycine), glucose metabolism (primed-constant infusion of [U- 14C]glucose and [6- 3H]glucose), and circulating hormone levels were measured during basal conditions within 48 to 60 hours after injury when the patients were receiving maintenance fluids without N or calories. Experimental data were analyzed as two groups (young, age 18 to 59, and elderly, age 60 to 85) and also as linear function of advancing age. The geriatric trauma (GT) group lost less N (11.9 ± 1.3 v 17.7 ± 1.7 g N/d, P = .025) than the younger group, mainly due to a significantly decreased whole-body protein breakdown (WBPB) rate. Despite a similar production and oxidation rate of glucose, hyperglycemia was more exaggerated in the elderly group. Advancing age resulted in significant positive correlations with plasma glucose levels and negative correlations with circulating growth hormone levels, urinary nitrogen loss, and protein turnover. These results suggest an age- and body composition-related reduced energy and protein metabolic response to severe trauma in elderly individuals.

Altered plasma free amino acid levels in obese traumatized man

Obesity is a major nutritional disorder that produces many abnormal metabolic responses. The effect of injury-induced stresses acting synergistically with the state of excessive body fat is not well known. Plasma levels of circulating free amino acids reflect the net status of protein breakdown and utilization. Hypoaminoacidemia is a common finding in severe injury and its significance in obese subjects was investigated. We measured in 10 obese (body mass index [BMI] > 30) and 10 non-obese (BMI < 30) traumatized (Injury Severity Score [ISS] 17 to 50) patients, the plasma levels of free amino acids in the early “flow” phase of injury when subjects were receiving maintenance fluids without calories or nitrogen. Postabsorptive control samples were obtained from 10 obese and 10 non-obese volunteers. Obese controls showed an increase in valine, leucine, isoleucine, and glutamic acid levels, and a decrease in glycine, tryptophan, threonine, histidine, taurine, citrulline, and cystine levels compared with lean controls. Hypoaminoacidemia was equally seen in traumatized obese and non-obese patients, and it was mainly due to a 24% decrease in nonessential amino acids. Remarkably, essential amino acid levels were the same in all groups. Arginine and ornithine levels were significantly different in traumatized obese compared with non-obese patients. The hypoglycinemia seen in non-obese trauma patients was absent in obese patients. The changes in levels of sulphur-containing amino acids also suggest that monitoring of these levels should be included in the nutritional management of obese trauma patients.

Obesity and the metabolic response to severe multiple trauma in man.

In the obese state profound metabolic disturbances exist and it is not known how this disrupted metabolism in obese subjects (body mass index greater than 30) may change their ability to respond to the superimposed, injury-induced stress. Understanding the mechanisms that modify the metabolic parameters in traumatized obese patients is essential in their nutritional assessment and further treatment. We have investigated in 7 obese and 10 nonobese multiple trauma patients, on a whole-body level, the energy metabolism, protein kinetics, and lipolysis in the early catabolic "flow phase" of severe injury when they were receiving maintenance fluids without calories or nitrogen. Traumatized obese patients mobilized relatively more protein and less fat compared with nonobese subjects. A relative block both in lipolysis and fat oxidation is experienced by injured obese patients that results in a shift to preferential use of proteins and carbohydrates. Reduced endogenous protein synthetic efficiency observed in obese patients implies increased protein recycling. Thus obese patients could not effectively use their most abundant fat fuel sources and have to depend on other fuel sources. The nutritional management of obese trauma victims should therefore be tailored towards provision of enough glucose calories to spare protein.

Effect of mannitol, nimodipine, and indomethacin singly or in combination on cerebral ischemia in rats.

The effects of mannitol, nimodipine, and indomethacin on ischemic neuronal injury were examined in 45 rats divided equally into nine groups subjected to 10 minutes of forebrain ischemia. Of two control groups, one received maintenance fluids while the other received a normal saline bolus. In the remaining seven groups, mannitol, nimodipine, and indomethacin were administered singly or in combination 5 minutes before forebrain ischemia. Seven days after ischemia, the brains were perfusion-fixed, sectioned coronally into 2.8-mm slices, and stained with hematoxylin and eosin. Ischemic neurons were directly counted on predetermined regions of standardized serial sections. Considerable amelioration of ischemic injury (ischemic neurons/total neurons) was observed with mannitol (ischemic injury, 7 +/- 5% in the hippocampal CA1/CA2 sectors and 28 +/- 17% in the CA3 sector). This is in contrast to control values of 64 +/- 11% and 80 +/- 6%, respectively, and those obtained in the normal saline group of 70 +/- 10% and 59 +/- 13%, respectively. The beneficial effect with nimodipine reached significance in only the hippocampal CA3 sector (ischemic injury, 35 +/- 21%). Indomethacin showed no significant benefit. Combining the agents resulted in significantly reduced neuronal injury compared with control groups, although the effect was not greater than that achieved with mannitol alone. The degree of ischemic injury was least when all three agents were used in combination (ischemic injury, 12 +/- 12% in the hippocampal CA1/CA2 sectors and 4 +/- 4% in the CA3 sector). Our data support the concept that successfully blocking the ischemic cascade with a single, diversely acting agent or multiple agents will evoke the best beneficial response.