Assessment of the Potential for Veverimer Drug-Drug Interactions.

Veverimer is a polymer being developed as a potential treatment of metabolic acidosis in patients with chronic kidney disease. Veverimer selectively binds and removes hydrochloric acid from the gastrointestinal tract, resulting in an increase in serum bicarbonate. Veverimer is not systemically absorbed, so potential drug-drug interactions (DDIs) are limited to effects on the absorption of other oral drugs through binding to veverimer in the gastrointestinal tract or increases in gastric pH caused by veverimer binding to hydrochloric acid. In in vitro binding experiments using a panel of 16 test drugs, no positively charged, neutral, or zwitterionic drugs bound to veverimer. Three negatively charged drugs (furosemide, aspirin, ethacrynic acid) bound to veverimer; however, this binding was reduced or eliminated in the presence of normal physiologic concentrations (100-170 mM) of chloride. Veverimer increased gastric pH in vivo by 1.5-3 pH units. This pH elevation peaked within 1 hour and had returned to baseline after 1.5-3 hours. Omeprazole did not alter the effect of veverimer on gastric pH. The clinical relevance of in vitro binding and the transient increase in gastric pH was evaluated in human DDI studies using two drugs with the most binding to veverimer (furosemide, aspirin) and two additional drugs with pH-dependent solubility effecting absorption (dabigatran, warfarin). None of the four drugs showed clinically meaningful DDI with veverimer in human studies. Based on the physicochemical characteristics of veverimer and results from in vitro and human studies, veverimer is unlikely to have significant DDIs. SIGNIFICANCE STATEMENT: Patients with chronic kidney disease, who are usually on many drugs, are vulnerable to drug-drug interactions (DDIs). The potential for DDIs with veverimer was evaluated based on the known site of action and physicochemical structure of the polymer, which restricts the compound to the gastrointestinal tract. Based on the findings from in vitro and human studies, we conclude that veverimer is unlikely to have clinically significant DDIs.

Reducing neonatal morbidity by discontinuing oxytocin during the active phase of first stage of labor: a multicenter randomized controlled trial STOPOXY.

BACKGROUND: Oxytocin is effective in reducing labor duration, but can be associated with fetal and maternal complications such as neonatal acidosis and post-partum hemorrhage. When comparing discontinuing oxytocin in the active phase with continuing oxytocin infusion, previous studies were underpowered to show a reduction in neonatal morbidity. Thus, we aim at evaluating the impact of discontinuing oxytocin during the active phase of the first stage of labor on the neonatal morbidity rate. METHODS: STOPOXY is a multicenter, randomized, open-label, controlled trial conducted in 20 maternity units in France. The first participant was recruited January 17th 2020. The trial includes women with a live term (≥37 weeks) singleton, in cephalic presentation, receiving oxytocin before 4 cm, after an induced or spontaneous labor. Women aged < 18 years, with a lack of social security coverage, a scarred uterus, a multiple pregnancy, a fetal congenital malformation, a growth retardation <3rd percentile or an abnormal fetal heart rate at randomization are excluded. Women are randomized before 6 cm when oxytocin is either continued or discontinued. Randomization is stratified by center and parity. The primary outcome, neonatal morbidity is assessed using a composite variable defined by an umbilical arterial pH at birth < 7.10 and/or a base excess > 10 mmol/L and/or umbilical arterial lactates> 7 mmol/L and/or a 5 min Apgar score < 7 and/or admission in neonatal intensive care unit. The primary outcome will be compared between the two groups using a chi-square test with a p-value of 0.05. Secondary outcomes include neonatal complications, duration of active phase, mode of delivery, fetal and maternal complications during labor and delivery, including cesarean delivery rate and postpartum hemorrhage, and birth experience. We aim at including 2475 women based on a reduction in neonatal morbidity from 8% in the control group to 5% in the experimental group, with a power of 80% and an alpha risk of 5%. DISCUSSION: Discontinuing oxytocin during the active phase of labor could improve both child health, by reducing moderate to severe neonatal morbidity, and maternal health by reducing cesarean delivery and postpartum hemorrhage rates. TRIAL REGISTRATION: Clinical trials NCT03991091 , registered June 19th, 2019.

Electrolyte and acid-base disorders in cancer patients and its impact on clinical outcomes: evidence from a real-world study in China.

Background: This study aims to delineate the incidence of electrolyte and acid-base disorders (EAD) in cancer patients, to figure out the risk factors of EAD, then to assess the impact of EAD on patients' in-hospital clinical outcomes.Methods: Patients with the diagnosis of malignancies hospitalized during 1 October 2014 and 30 September 2015 were recruited in Zhongshan Hospital, Fudan University in Shanghai of China. Demographic characteristics, comorbidities, and clinical data, including survival, length of stay and hospital cost, were extracted from the electronic medical record system. Electrolyte and acid-base data were acquired from the hospital laboratory database.Results: Of 25,881 cancer patients with electrolyte data, 15,000 (58.0%) cases had at least one electrolyte and acid-base abnormity. Hypocalcemia (27.8%) was the most common electrolyte disorder, followed by hypophosphatemia (26.7%), hypochloremia (24.5%) and hyponatremia (22.5%). The incidence of simple metabolic acidosis (MAC) and metabolic alkalosis (MAL) was 12.8% and 22.1% respectively. Patients with mixed metabolic acid-base disorders (MAC + MAL) accounted for 30.2%. Lower BMI score, preexisting hypertension and diabetes, renal dysfunction, receiving surgery/chemotherapy, anemia and hypoalbuminemia were screened out as the major risk factors of EAD. In-hospital mortality in patients with EAD was 2.1% as compared to those with normal electrolytes (0.3%). The risk of death significantly increased among patients with severe EAD. Similarly, the length of stay and hospital cost also tripled as the number and grade of EAD increased.Conclusion: EAD is commonly encountered in cancer patients and associated with an ominous prognosis. Patients with comorbidities, renal/liver dysfunction, and anti-tumor therapy have a higher risk of EAD. Regular monitoring of electrolytes, optimum regimen for intravenous infusion, timely correction of modifiable factors and appropriate management of EAD should not be neglected during anti-tumor treatment.

The Prevalence and Management of Metabolic Acidosis of Chronic Kidney Disease

Aim Emerging evidence supports initiating oral sodium bicarbonate (OSB) at a serum bicarbonate (HCO3) level of less than 22mmol/L. We look to identify the prevalence of metabolic acidosis of chronic kidney disease (MA-CKD) and its management with OSB at a regional university hospital. Methods Retrospective data was collected using the national electronic renal database (eMED) to identify chronic kidney disease (CKD) patients with MA-CKD over a one-year period. Results One-hundred and forty-four patients were identified with CKD, of which 131 (89%) were tested for HCO3. MA-CKD was present in 44 patients (34%), all had eGFR< 30ml/min/1.73m2, 7 (16%) were prescribed OSB, 7(16%) OSB was contraindicated, and 37 (84%) patients managed with dietary input only. Mean HCO3 level at initiation in OSB group was 18.3±1mmol/L compared to 19.4±1.4mmol/L in dietary input only group which was statistically significant (p<0.05). Conclusion A high burden of advanced CKD was found in the regional nephrology centre, with one third of patients demonstrating MA-CKD. Majority had dietary input only. Further awareness and consensus need to be established on the benefits of treating MA-CKD with OSB.

Assessment of resuscitation as measured by markers of metabolic acidosis and features of injury.

AIMS: The best time for definitive orthopaedic care is often unclear in patients with multiple injuries. The objective of this study was make a prospective assessment of the safety of our early appropriate care (EAC) strategy and to evaluate the potential benefit of additional laboratory data to determine readiness for surgery. PATIENTS AND METHODS: A cohort of 335 patients with fractures of the pelvis, acetabulum, femur, or spine were included. Patients underwent definitive fixation within 36 hours if one of the following three parameters were met: lactate < 4.0 mmol/L; pH ≥ 7.25; or base excess (BE) ≥ -5.5 mmol/L. If all three parameters were met, resuscitation was designated full protocol resuscitation (FPR). If less than all three parameters were met, it was designated an incomplete protocol resuscitation (IPR). Complications were assessed by an independent adjudication committee and included infection; sepsis; PE/DVT; organ failure; pneumonia, and acute respiratory distress syndrome (ARDS). RESULTS: In total, 66 patients (19.7%) developed 90 complications. An historical cohort of 1441 patients had a complication rate of 22.1%. The complication rate for patients with only one EAC parameter at the point of protocol was 34.3%, which was higher than other groups (p = 0.041). Patients who had IPR did not have significantly more complications (31.8%) than those who had FPR (22.6%; p = 0.078). Regression analysis showed male gender and injury severity score to be independent predictors of complications. CONCLUSIONS: This study highlights important trends in the IPR and FPR groups, suggesting that differences in resuscitation parameters may guide care in certain patients; further study is, however, required. We advocate the use of the existing protocol, while research is continued for high-risk subgroups. Cite this article: Bone Joint J 2017;99-B:122-7.

Indicators of induced subacute ruminal acidosis (SARA) in Danish Holstein cows.

BACKGROUND: The prevalence of subacute ruminal acidosis (SARA) in dairy cows is high with large impact on economy and welfare. Its current field diagnosis is based on point ruminal pH measurements by oral probe or rumenocentesis. These techniques are invasive and inaccurate, and better markers for the diagnosis of SARA are needed. The goal of this study was to evaluate clinical signs of SARA and to investigate the use of blood, faecal and urinary parameters as indicators of SARA. Six lactating, rumen cannulated, Danish Holstein cows were used in a cross-over study with three periods. The first and second periods included two cows on control diet and two cows on nutritional SARA challenge. The third period only included two cows on SARA challenge. Control diet was a conventional total mixed ration [45.5% dry matter (DM), 17.8% crude protein, 43.8% neutral detergent fibre, and 22.5% acid detergent fibre (DM basis)]. SARA challenge was conducted by substituting control diet with grain pellets (50% wheat/barley) over 3 days to reach 40% grain in the diet. Ruminal pH was measured continuously. Blood samples were collected once daily at 7 h after feeding. Samples of faeces and urine were collected at feeding, and at 7 and 12 h after feeding. Blood samples were analysed for pCO2, pO2, pH, electrolytes, lactate, glucose, packed cell volume (PCV), and total plasma protein concentration. Milk composition, ruminal VFA, and pH of faeces and urine were measured. RESULTS: SARA was associated with decreased (P < 0.05) minimum ruminal, faecal and urinary pH. Daily times and areas of ruminal pH below 5.8, and 5.6 were increased to levels representative for SARA. Significant differences were detected in milk composition and ruminal VFAs. Blood calcium concentration was decreased (P < 0.05), and pCO2 tended to be increased (P = 0.10). Significant differences were not detected in other parameters. CONCLUSIONS: SARA challenge was associated with changes in faecal and urinary pH, blood calcium concentration and pCO2. These may be helpful as indicators of SARA. However changes were small, and diurnal variations were present. None of these parameters are able to stand alone as indicators of SARA.

[Usefulness of blood formic acid detection in the methanol poisoning in the practice of clinical toxicology department-preliminary assessment]. / Ocena wstepna przydatnosci oznaczenia kwasu mrówkowego w diagnostyce zatruc metanolem w praktyce oddzialu toksykologii klinicznej.

BACKGROUND: Severe metabolic acidosis is one of the most difficult diagnostic and therapeutic challenges. The most common causes of this type of acid-base balance disorder are toxic alcohols, e.g. methanol poisoning. Metabolites of methanol, formaldehyde and formic acid are responsible for severe symptoms of this poisoning. OBJECTIVE: The aim of this study is a preliminary assessment of usefulness of formic acid detection by gas chromatography in the daily practice of clinical toxicology department in methanol poisoning confirmed by the designation of this alcohol in the blood. METHODS: The study included 9 patients from Greater Poland region diagnosed with methanol poisoning. Blood samples were collected during routine laboratory tests, on admission secured at-80°C, and then formic acid was determined by head-space gas chromatography. The relationship between the concentration of blood formic acid and methanol, ethanol, and the acid-base balance parameters were evaluated. RESULTS: The study group consisted of 9 men, aged 49.89 ± 6.17 years. All patients were diagnosed with alcohol dependence. In most cases (66.67%) and methanol poisoning occurred during ethanol abuse. The average blood methanol and ethanol concentrations were 2.48±1.74 g/L and 0.99±1.73 g/L respectively. The average blood formic acid concentration was 0.59±0.46 g/L, from 0.0 to 1.12 g/L. Acid-base balance parameters were (mean± SD): pH 7.00 ±0.36; pCO2 32.26 ± 14.54 mmHg; PO2 114.24±77.53 mmHg; BE -18.28 16.76 mmol/L; HCO3-12.70±11.53 mmol/L. There was a positive correlation be- tween the blood methanol and formic acid concentration. A negative correlation was found between the blood ethanol and formic acid concentration. In patients with positive blood ethanol concentration (1.74 to 5.0 g/L, mean 2.96±1.78 g/L) there was not any formic acid, despite the presence of methanol was confirmed. These patients did not demonstrate metabolic acidosis (mean±SD): pH 7.43 ±0.20; HCO3- 27.87 ± 2.36 mmol/L; BE 3.60 ±2.40 mmol/L. In contrast, in all patients with negative blood ethanol concentration, tests confirmed metabolic acidosis and elevated formic acid (mean SD): pH 6.80±0.20; HCO3- 5.12±1.67 mmol/L; BE-29.20±3.68 mmol/L; formic acid 0.89±0.16 g/L. CONCLUSION: Methanol poisoning cannot be confirmed by positive blood formic acid in patients with high blood ethanol concentration (≥1.74 g/L). In this kind of intoxication severe metabolic acidosis does not occur too. In patients with no detectable blood ethanol concentration, blood formic acid concentration can reach 1.12 g/L and correlates with the severity of metabolic acidosis.

Dietary electrolyte balance affects the nutrient digestibility and maintenance energy expenditure of Nile tilapia.

Acid-base disturbances caused by environmental factors and physiological events including feeding have been well documented in several fish species, but little is known about the impact of dietary electrolyte balance (dEB). In the present study, we investigated the effect of feeding diets differing in dEB (-100, 200, 500 or 800 mEq/kg diet) on the growth, nutrient digestibility and energy balance of Nile tilapia. After 5 weeks on the test diet, the growth of the fish was linearly affected by the dEB levels (P< 0·001), with the lowest growth being observed in the fish fed the 800 dEB diet. The apparent digestibility coefficient (ADC) of fat was unaffected by dEB, whereas the ADC of DM and protein were curvilinearly related to the dEB levels, being lowest and highest in the 200 and 800 dEB diets, respectively. Stomach chyme pH at 3 h after feeding was linearly related to the dEB levels (P< 0·05). At the same time, blood pH of the heart (P< 0·05) and caudal vein (P< 0·01) was curvilinearly related to the dEB levels, suggesting the influence of dEB on postprandial metabolic alkalosis. Consequently, maintenance energy expenditure (MEm) was curvilinearly related to the dEB levels (P< 0·001), being 54 % higher in the 800 dEB group (88 kJ/kg(0·8) per d) than in the 200 dEB group (57 kJ/kg(0·8) per d). These results suggest that varying dEB levels in a diet have both positive and negative effects on fish. On the one hand, they improve nutrient digestibility; on the other hand, they challenge the acid-base homeostasis (pH) of fish, causing an increase in MEm, and thereby reduce the energy required for growth.

RETRACTED: Modified U-shaped ileal neobladder after radical cystectomy: assessment of functional outcomes and complications in Chinese patients.

This article has been retracted: please see Elsevier Policy on Article Withdrawal (http://www.elsevier.com/locate/withdrawalpolicy). This article has been retracted at the request of the Editor-in-Chief. After investigation, it was confirmed that there were considerably fewer cases with modified U-shaped ileal neobladder at the research institution than was written about in the manuscript.

[Does Stewart-Fencl improve the evaluation of acid-base status in stable patients on hemodiafiltration?]. / ¿Mejora la aproximación físico-química de Stewart-Fencl la valoración del equilibrio ácido-base en pacientes estables en hemodiafiltración?

INTRODUCTION: The traditional evaluation of acid-base status relies on the Henderson-Hasselbach equation. In 1983, an alternative approach, based on physical and chemical principles was proposed by P. Stewart. In this approach, plasma pH is determined by 3 independent variables: pCO2, Strong Ion Difference (SIDm), which is the difference between the strong cations (Na +, K +, Ca ++, Mg ++) and the strong anions (Cl-, lactate) and total plasma concentration of nonvolatile weak acids (ATot), mainly inorganic phosphate and albumin. Bicarbonate is considered a dependent variable. The aim of this study was to evaluate the acid-base status using both perspectives, physical chemical and traditional approach. MATERIAL AND METHODS: We studied 35 patients (24 M; 11F) on hemodiafiltration, mean age was 67,2+/-15,7, 8+/-19,2 kg. We analyzed plasma chemistry including pH, pCO2, HCO3-, base excess and Na+, K+, Cl-, Ca++, Mg++, lactate and SIDm. The SID estimated (SIDe) was calculated by Figge's formula (1000 x 2.46E-11 x pCO2 / (10-pH) + Album gr/dl x (0.123 x pH-0.631) + P in mmol/l x (0.309 x pH-0.469) and Gap of the SID as the difference SIDm-SIDe. RESULTS: pH preHD was 7,36+/-0,08 and pH posHD 7,44+/-0,08 (p < 0.001). There was no significant differences between pCO2 pre and pos-HD. HCO3 - and base excess increased during the session (p < 0.001). SIDm decreased from 46,2+/-2,9 preHD to 45+/-2,3 mEq/l postHD (p < 0.05). On the opposite, SIDe increased from 38,5+/-3,8 to 42,9+/-3,1 mEq/l (p < 0.001). The Gap Anion descended from 18,6+/-3,8 preHD to 12,8+/-2,8 mEq/l mEq/l postHD (p < 0.001) and the Gap of the SID 7,6+/-3 to 2,1+/-2 (p < 0.001). Anion Gap correlated with the Gap-SID so much pre-HDF as pos-HDF. Delta Base excess correlated only with Delta of the Gap SID. CONCLUSION: Stewart-Fencl's approach does not improve characterization of acid-base status in patients on chronic HDF. In presence of normocloremia the SIDm does not reflect the alkalinizing process of the session of hemodialysis. According this approach, hemodialysis therapy can be viewed as a withdrawal of inorganic anions, especially the sulphate. These anions are replaced by OH - and secondarily for HCO3-. The approach only improves the evaluation of unmeasured anions by the Gap of the SID, without the effect of albumin and phosphate.

Damage control orthopaedics: lessons learned.

Damage control orthopaedics (DCO) is a staged approach for the management of multiply injured patients. It is ideal for trauma patients presenting in an unstable or extremis physiological state. It focuses on the rapid resuscitation of these patients by providing temporary stabilisation of fractures while at the same time reducing the biological load of surgery. Early findings support its usefulness in controlling the lethal triad of hypothermia, acidosis and coagulopathy. Furthermore, recent evidence indicates that it regulates the evolving systemic inflammatory response, reducing the detrimental complications of adult respiratory distress syndrome, multiple organ dysfunction and subsequent mortality. Although DCO has been proven a useful surgical strategy for efficiently managing patients with multiple trauma, further work is required to establish fully its indications, results and cost implications.

Impact of intraoperative myocardial tissue acidosis on postoperative adverse outcomes and cost of care for patients undergoing prolonged aortic clamping during cardiopulmonary bypass.

BACKGROUND: This study examined the impact of intraoperative myocardial acidosis and adverse postoperative outcomes on the cost of cardiac surgical care. METHODS: Myocardial tissue pH corrected to 37 degrees C (pH(37C)) was measured in 162 patients with cross-clamp (XC) duration of 119 minutes or longer. Perioperative data and outcomes were collected prospectively. The Veterans Affairs cost accounting system was used to determine the cost of care in a subset of 57 patients. RESULTS: Long XC duration was associated with significantly increased acidosis and adverse postoperative outcomes. The cost of care for patients with adverse outcomes was increased by 110% (P < .0001). Patients with acidosis at the end of reperfusion had significantly (P = .0470) increased costs of care. End reperfusion of myocardial tissue pH(37C) of less than 7.0, diabetes mellitus, and body surface area were significant determinants of postoperative adverse outcomes. CONCLUSIONS: Intraoperative myocardial acidosis is a determinant of postoperative adverse outcomes and cost in cardiac surgery. Reducing XC duration and improving intraoperative myocardial protection should improve outcomes and reduce cost.

Combat damage control surgery.

BACKGROUND: Although the use of damage control surgery for blunt and penetrating injury has been widely reported and defined, the use of damage control surgery on the battlefield (combat damage control surgery) has not been well detailed. DISCUSSION: Damage control surgery is now well established as the standard of care for severely injured civilian patients requiring emergent laparotomy in the United States. The civilian damage control paradigm is based on a "damage control trilogy." This trilogy comprises an abbreviated operation, intensive care unit resuscitation, and a return to the operating room for the definitive operation. The goal of damage control surgery and the triology is avoidance of irreversible physiological insult termed the lethal triad. The lethal triad comprises the vicious cycle of hypothermia, acidosis, and coagulopathy. Although the damage control model involves the damage control trilogy, abbreviated operation, intensive care unit resuscitation, and definitive operation, all in the same surgical facility, the combat damage control paradigm must incorporate global evacuation through several military surgical facilities and involves up to ten stages to allow for battlefield evacuation, surgical operations, multiple resuscitations, and transcontinental transport. SUMMARY: Combat damage control surgery represents many unique challenges for those who care for the severely injured patients in a combat zone.

A randomised clinical trial on cardiotocography plus fetal blood sampling versus cardiotocography plus ST-analysis of the fetal electrocardiogram (STAN) for intrapartum monitoring.

BACKGROUND: Cardiotocography (CTG) is worldwide the method for fetal surveillance during labour. However, CTG alone shows many false positive test results and without fetal blood sampling (FBS), it results in an increase in operative deliveries without improvement of fetal outcome. FBS requires additional expertise, is invasive and has often to be repeated during labour. Two clinical trials have shown that a combination of CTG and ST-analysis of the fetal electrocardiogram (ECG) reduces the rates of metabolic acidosis and instrumental delivery. However, in both trials FBS was still performed in the ST-analysis arm, and it is therefore still unknown if the observed results were indeed due to the ST-analysis or to the use of FBS in combination with ST-analysis. METHODS/DESIGN: We aim to evaluate the effectiveness of non-invasive monitoring (CTG + ST-analysis) as compared to normal care (CTG + FBS), in a multicentre randomised clinical trial setting. Secondary aims are: 1) to judge whether ST-analysis of fetal electrocardiogram can significantly decrease frequency of performance of FBS or even replace it; 2) perform a cost analysis to establish the economic impact of the two treatment options. Women in labour with a gestational age > or = 36 weeks and an indication for CTG-monitoring can be included in the trial. Eligible women will be randomised for fetal surveillance with CTG and, if necessary, FBS or CTG combined with ST-analysis of the fetal ECG. The primary outcome of the study is the incidence of serious metabolic acidosis (defined as pH < 7.05 and Bdecf > 12 mmol/L in the umbilical cord artery). Secondary outcome measures are: instrumental delivery, neonatal outcome (Apgar score, admission to a neonatal ward), incidence of performance of FBS in both arms and cost-effectiveness of both monitoring strategies across hospitals. The analysis will follow the intention to treat principle. The incidence of metabolic acidosis will be compared across both groups. Assuming a reduction of metabolic acidosis from 3.5% to 2.1 %, using a two-sided test with an alpha of 0.05 and a power of 0.80, in favour of CTG plus ST-analysis, about 5100 women have to be randomised. Furthermore, the cost-effectiveness of CTG and ST-analysis as compared to CTG and FBS will be studied. DISCUSSION: This study will provide data about the use of intrapartum ST-analysis with a strict protocol for performance of FBS to limit its incidence. We aim to clarify to what extent intrapartum ST-analysis can be used without the performance of FBS and in which cases FBS is still needed. TRIAL REGISTRATION NUMBER: ISRCTN95732366.

Complex therapy for hepatic trauma.

OBJECTIVE: To investigate the optimal surgical management of patients with hepatic trauma. DESIGN: A retrospective analysis of 197 patients treated for hepatic trauma in the two hospitals from January 1980 to January 2001. SETTING: Qilu and Dodoma Hospital in China and Tanzania respectively. PATIENT INTERVENTIONS: Two patients died before surgery, seven patients were treated conservatively, while 188 patients underwent various surgical interventions under the principles of damage control surgery including initial laparotomy, resuscitation phase and definitive surgery. RESULTS: The overall mortality was 15.3% (30/197). The leading cause of death was the triad of coagulopathy, hypothermia and metabolic acidosis. CONCLUSION: Patients with major exanguinating injuries will not survive complex procedures such as formal hepatic resection or complex procedures such as formal hepatic resection or pancreaticoduodenectomy. The operating team must undergo a radical shift in their "surgical ideology" if the patient is to survive such devastating injuries. The central principle of damage control surgery is that patients died of the triad of coagulopathy, hypothermia and metabolic acidosis. Damage control surgery can be thought of in three distinct phases: initial truncated laparotomy, resuscitation phase and definitive operation.

Assessment of acid-base status of cats with naturally occurring chronic renal failure.

Metabolic acidosis is reported to be a common complication of feline chronic renal failure (CRF) but acid-base status of feline patients with this disease is rarely assessed by general practitioners. A cross-sectional study involving 59 cases of naturally occurring feline CRF was conducted to determine the prevalence of acid-base disturbances. Cases were categorised on the basis of their plasma creatinine concentrations as mild, moderate or severe. A group of 27 clinically healthy, age-matched cats was assessed for comparison. A low venous blood pH (<7.270) was found in 10 of the 19 severe cases (52.6 per cent), three of the 20 moderate cases (15 per cent) and none of the 20 mild cases. Acidaemia was associated with an increased anion gap contributed to by both low plasma bicarbonate and low chloride ion concentrations. Biochemical analysis of urine samples showed urine pH to decrease with increasing severity of renal failure. Urinary loss of bicarbonate was not associated with the occurrence of acidaemia and there was a tendency for urinary ammonium ion excretion to decrease as the severity of renal failure increased. Cats with naturally occurring CRF do not show plasma biochemical evidence of acid-base disturbances until the disease is advanced.

Hemofiltration and peritoneal dialysis in infection-associated acute renal failure in Vietnam.

BACKGROUND: In some parts of the world, peritoneal dialysis is widely used for renal replacement in acute renal failure. In resource-rich countries, it has been supplanted in recent years by hemodialysis and, most recently, by hemofiltration and associated techniques. The relative efficacy of peritoneal dialysis and hemofiltration is not known. METHODS: We conducted an open, randomized comparison of pumped venovenous hemofiltration and peritoneal dialysis in patients with infection-associated acute renal failure in an infectious-disease referral hospital in Vietnam. RESULTS: Seventy adult patients with severe falciparum malaria (48 patients) or sepsis (22 patients) were enrolled; 34 were assigned to hemofiltration and 36 to peritoneal dialysis. The mortality rate was 47 percent (17 patients) in the group assigned to peritoneal dialysis, as compared with 15 percent (5 patients) in the group assigned to hemofiltration (P=0.005). The rates of resolution of acidosis and of decline in the serum creatinine concentration in the group assigned to hemofiltration were more than twice those in the group assigned to peritoneal dialysis (P<0.005), and renal-replacement therapy was required for a significantly shorter period. In a multivariate analysis, the odds ratio for death was 5.1 (95 percent confidence interval, 1.6 to 16) and that for a need for future dialysis was 4.7 (95 percent confidence interval, 1.3 to 17) in the group assigned to peritoneal dialysis. The cost of hemofiltration per survivor was less than half that of peritoneal dialysis, and the cost per life saved was less than one third. CONCLUSIONS: Hemofiltration is superior to peritoneal dialysis in the treatment of infection-associated acute renal failure.

Daily and nocturnal hemodialysis: how do they stack up?

A growing number of articles in the literature describe experiences using more frequent hemodialysis (HD), either short daily or long nocturnal. Most of these publications highlight successes obtained by these programs with a fragmented look at specific areas and outcomes. This review of published results from the use of these therapies shows that universal improvement is noted in dialysis adequacy, nutrition, quality of life, blood pressure control, fluid and electrolyte balance, and hospitalizations when these parameters are mentioned. However, data reporting is often incomplete. Most studies do not have adequate control groups, patient populations are often different from the standard HD population, and many have small numbers that preclude statistical significance. Nonuniformity of patient selection and study design prevents accurate comparison and pooling of patient data. In some cases, the same patients' data for the same periods of observation are reported in several studies. Despite data that can be characterized as preliminary and anecdotal, the results reported in this review show remarkable patient improvement worthy of serious consideration by the renal community. To reach a level of evidence that will be widely acceptable, the renal community needs to partner with such government institutions as the National Institutes of Health and the Health Care Financing Administration to study systematically the outcomes and costs associated with using more frequent HD. In the process, important ramifications of such a cooperative study, including potential changes in policy, need to be considered.

Assessment of hemodynamic and gastric mucosal acidosis with modified fluid versus 6% hydroxyethyl starch: a prospective, randomized study.

OBJECTIVE: To investigate the effect of 4 % succinylated modified fluid gelatin (MFG) versus mean weight, highly substituted 6% hydroxyethyl starch (HES) on hemodynamic and gastric mucosal acidosis variables, in septic hypovolemic patients. DESIGN: Prospective, randomized, clinical investigation. SETTING: University hospital intensive care unit. PATIENTS: Thirty-four septic hypovolemic ventilated and hemodynamically controlled patients. INTERVENTIONS: Invasive hemodynamic and gastric tonometric measurements. MEASUREMENTS AND RESULTS: Hemodynamic and tonometric parameters were recorded at baseline and 60 min after infusion of 500 ml of each colloid. In all patients central venous pressure, pulmonary artery occlusion pressure, cardiac index and mean arterial pressure increased significantly with both colloids, and hemoglobin concentration decreased by the same amount while oxygen delivery remained stable. Gastric intramucosal pH increased from 7.27 +/- 0.08 to 7.31 +/- 0.07 (p < 0.001) with MFG and decreased non-significantly from 7.26 +/- 0.11 to 7.22 +/- 0.08 (ns) with HES. Carbon dioxide gastric mucosal arterial gradient decreased from 18 +/- 9 to 13 +/- 9 mmHg (p < 0.0005) in the MFG group and rose non-significantly from 18 +/- 11 to 21 +/- 11 mmHg with HES. CONCLUSIONS: Although MFG and 6% HES have the same hemodynamic effects, their physicochemical properties induce different responses on gastric mucosal acidosis in septic, hypovolemic and ventilated patients. These effects of MFG and HES on gastric mucosa need to be considered in patient management.

Clinical application of cerebrovascular reserve assessment as a strategy for stroke prevention.

Patients diagnosed as having symptomatic carotid occlusion, who are at increased risk for stroke, can be readily identified by methods designed to measure cerebrovascular reserves. This paper reviews the use of xenon-enhanced computed tomography (Xe/CT) cerebral blood flow (CBF) methods for quantitatively assessing cerebrovascular reserves.