Point-of-care blood gas analysers: a performance evaluation.

Neonates represent a group with unusual sample characteristics and tend to have high hematocrits (Hct). The critically ill patient is also far from ideal with respect to sample type, being prone to either hemodilution or hemoconcentration. Prior to the selection of a point-of-care testing (POCT) analyser for blood gases and electrolytes, we therefore undertook a careful evaluation of some of the performance characteristics of selected instruments. We also conducted an evaluation of one of these systems using patients in the operating room (OR) and the pediatric Intensive Care Unit (ICU). Overall performance for hematocrit determination was acceptable in middle ranges but showed bias at high and low extremes. One system showed significant bias for electrolytes. For the patient evaluation, the system tested, the ABL70 (Radiometer, Copenhagen), showed a small positive bias for Na determinations. It also showed an important bias for pO(2) at levels that are clinically significant. The possibility of operator-related effects on test results has to be eliminated. In terms of ease of use and client satisfaction, the system was well received.

Status of point-of-care testing: promise, realities, and possibilities.

Point-of-care testing (POCT) has evolved from the demand for analytical information more rapidly than is available from central laboratories. By bringing the analysis closer to the patient several process steps have been eliminated, facilitating a shorter time to result and faster management response with improved outcomes. Thus benefits include better therapeutic turnaround times, decreased blood loss as a result of reduced phlebotomy secondary to clinical improvement, and diminished resource utilization. These advantages depend on acceptable analytical performance in comparison with central laboratory methods and in relation to clinical criteria. Generally these requirements are met but there are problems particularly with atypical specimens. Outcomes and cost-benefit analyses have been difficult to perform and evaluate. Given the multitude of participants, quality assurance and program management are recognized as resource intensive. However, recognition of problem areas is driving continuous improvement and we envisage expansion of this paradigm.

Elevated serum cytokines are associated with cytomegalovirus infection and disease in bone marrow transplant recipients.

To assess the relationship between serum cytokines and cytomegalovirus (CMV) reactivation, 75 allogeneic bone marrow transplant patients underwent weekly measurements of interleukin (IL)-6, IL-8, and tumor necrosis factor (TNF)-alpha, CMV blood cultures, and antigenemia tests. Of the patients, 44 (58.7%) developed CMV infection, and 19 (25.3%) developed clinical CMV disease. The mean maximum levels of all three cytokines were significantly increased in patients with CMV infection compared with levels in those without. Maximum levels of IL-6 were significantly higher in patients with active CMV disease than in those who did not develop CMV disease (281.2+/-85.5 vs. 95.7+/-15.0 pg/mL; P=.034). Levels of IL-8 and TNF-alpha were also elevated in patients who developed active disease. In a multivariate logistic regression model, IL-6 levels were independently associated with CMV disease (odds ratio=1.70 per 100-pg/mL increase in IL-6; P=.009). Cytokines may play an important role in the pathogenesis of CMV after bone marrow transplantation and may be a useful predictor for CMV.

Nutricel as an additive solution for neonatal transfusion.

Red cell concentrates stored in additive solutions have limitations for use in the pediatric population. Our survey of 10 pediatric institutions found that Nutricel supernatant was often removed prior to infusion. Examination of packed red cells showed a potassium concentration in excess of 15 mmol/l by day 7 in AS-3 and 40 mmol/l by day 35. Comparison with cells stored in CP2D and CPDA1 showed that the total mass of potassium was highest in AS-3 (5.6 mmol/l) as was the phosphate. The total mass of citrate and glucose was considerably increased in the AS-3 system at 1.73 mmoles and 3.23 mmoles. All had a pH less than 6.6 at day 35. The high concentration of potassium in AS-3 raises concern for the potential for hyperkalemic dysrhythmias during massive transfusion while the citrate load has clinical implications for divalent cation homeostasis during rapid infusion or exchange; the glucose may induce hyperglycemic sequelae.

Reduction of plasma volume after storage of platelets in CP2D.

BACKGROUND: There has been concern that further deterioration might occur if stored platelets are centrifuged to reduce their volume. Although such centrifugation appears to have minimal effect on platelets in CPDA-1 (osmolarity, 470 mOsm) there is no information on the situation with CP2D (580 mOsm). STUDY DESIGN AND METHODS: Platelet concentrates from CP2D packs were sampled at 1 and 5 days and after centrifugation was used to reduce the plasma volume to 10 mL. The aggregation, hypotonic shock response, morphology, pH, and lactate, glucose, pCO2 and pO2 levels were assessed, and values were compared to those seen with CPDA-1. In addition, blood was collected from the same donors into both CP2D and standard sodium citrate anticoagulant in an anticoagulant-to-blood ratio of 1:8 and the aggregation response of the fresh platelets was measured. RESULTS: Collection of blood into CP2D results in an immediate reduction of the platelet aggregation response when compared to that found after collection of blood into sodium citrate or CPDA-1. Aggregation is further decreased after storage; however, these changes and those for hypotonic shock, pH, lactate, glucose, and pCO2 are similar to those seen for CPDA-1. Additional centrifugation did not cause further change. CONCLUSION: Platelets stored in CP2D have reduced in vitro function after 5 days of storage, but subsequent centrifugation to reduce the plasma volume does not further alter these platelets.

The efficacy of diazepam in the treatment of acute iron overload in rats.

While conducting studies on the prevention of mortality from acute iron intoxication in rats, diazepam, given to prevent animal suffering, was observed to be associated with reduced mortality in a limited number of animals. The objective was to assess whether diazepam reduces mortality following acute iron intoxication in rats. Survival of rats was compared among groups receiving (i) orally 612 mg/kg iron alone (LD60), (ii) iron with a subcutaneous injection of 2.5 mg/kg diazepam (DZ), or (iii) iron, DZ with 800 mg/kg deferiprone intraperitoneal injections. The administration of DZ decreased mortality from 60 to 16% (p < 0.001). The addition of deferiprone to DZ resulted in zero mortality (p < 0.05 compared with the DZ group) over the study period. The administration of DZ was not associated with decreased iron absorption or increased urinary iron excretion, whereas the administration of deferiprone did result in urinary iron excretion. Microscopic examination suggests that diazepam administration may be associated with lower intracellular accumulation of iron. In conclusion, diazepam reduces mortality from iron overdose in rats through a yet unidentified mechanism, although the drug does not inhibit iron absorption or enhance urinary iron removal.

Subarachnoid hemorrhage in the African-American population: a cooperative study.

The clinical outcome of patients following subarachnoid hemorrhage is complicated by delayed cerebral ischemia and contributing factors such as hypertension. To observe the impact of hypertension and delayed cerebral ischemia on the outcome of a predominantly African-American cohort following subarachnoid hemorrhage, both retrospective (n = 42) and prospective (n = 21) studies were conducted. In the total pool (n = 63), the mean age was 49.7 years (range: 17 to 80) with a preponderance of female patients (70%). Aneurysm formation was significant in the region of the posterior communicating artery. Of the patients reviewed, 73.8% had preexisting hypertension and 45.9% developed delayed cerebral ischemia. Approximately 89% of the patients who suffered from delayed cerebral ischemia had hypertension. Results failed to display any significant beneficial association between the use of the calcium channel blocker nimodipine and delayed cerebral ischemia. Use of the antifibrinolytic drug aminocaproic acid demonstrated a worse patient outcome. It is not recommended that aminocaproic acid be used in this population. Subsequently, due to the proportional occurrence of delayed cerebral ischemia in hypertensive patients following subarachnoid hemorrhage, it is suggested that prophylactic surgical management of unruptured intracranial aneurysms be considered in hypertensive patients. Further study is needed to discern the association between hypertension, delayed cerebral ischemia, and stroke in patients following subarachnoid hemorrhage.

The neuromuscular effects of mivacurium chloride during propofol anesthesia in children.

Previous studies examined the neuromuscular effects of mivacurium in doses up to, but not exceeding, 2.5 times 95% effective dose (ED95) in children. To determine whether larger doses offer clinical advantages, we compared the onset and duration of neuromuscular block, intubating conditions, and changes in plasma histamine concentration (PHC) after mivacurium (0.2, 0.3, or 0.4 mg/kg) with those after succinylcholine (2.0 mg/kg) during propofol/N2O anesthesia in 48 children aged 3-10 yr. The evoked electromyograph (EMG) of the adductor digiti minimi after supramaximal train-of-four (TOF) stimulation was recorded. When T1 was 10% of control, laryngoscopy and intubation were performed. PHC was measured immediately before and at 2 and 5 min after administration of the relaxant. Venous blood was sampled for determination of plasma cholinesterase activity. Axillary temperature was measured. Increasing the dose of mivacurium from 0.2 to 0.3 mg/kg accelerated the onset of block (time to 90% block, 1.6 +/- 0.2 vs 1.2 +/- 0.2 min) (P < 0.001), but did not significantly prolong recovery (time to 95% recovery, 16.0 +/- 3.8 vs 18.6 +/- 3.6 min). A further increase in dose to 0.4 mg/kg produced no significant decrement in onset time, but did prolong recovery (time to 95% recovery, 23.8 +/- 5.0 min) (P < 0.001). The duration of action of mivacurium 0.3 and 0.4 mg/kg correlated inversely with plasma cholinesterase activity. PHC increased significantly after mivacurium 0.3 and 0.4 mg/kg; however, mean arterial pressure did not change significantly. We conclude that mivacurium 0.3 mg/kg provides a relatively rapid onset and short duration of neuromuscular block in healthy children. Increasing the dose to 0.4 mg/kg does not significantly accelerate the onset of neuromuscular block.

Interference in glucose and other clinical chemistry assays by thiocyanate and cyanide in a patient treated with nitroprusside.

A 3-year-old patient treated with nitroprusside for congestive heart failure had 6.5 mmol/L thiocyanate (toxic, >1.5 mmol/L) and 110 micromol/L cyanide (toxic, >5 micromol/L) present in her blood. At this time a whole-blood glucose concentration assayed on the Nova Stat Profile 5 Plus (Stat Profile) was 25.1 mmol/L. Plasma from that specimen analyzed on a Kodak Ektachem 700 analyzer (E700) indicated 5.2 mmol/L glucose. We investigated the potential interference of dissolved thiocyanate or cyanide on glucose and other routine assays. Toxic concentrations of thiocyanate increased Stat Profile glucose values and E700 total calcium, chloride, and creatinine values. Stat Profile ionized calcium values were decreased by toxic concentrations of thiocyanate. Cyanide (100 micromol/L) decreased alanine aminotransferase activity measured on the E700. Interference with the Stat Profile glucose assay may have been caused by thiocyanate oxidation at the glucose electrode.

Efficacy of deferiprone in the treatment of acute iron intoxication in rats.

BACKGROUND: Deferiprone [(1,2-dimethyl-3-hydroxypyrid-4-one) (L1)], is the first orally active iron chelating agent to reach clinical trials in patients with chronic iron overload. Its efficacy in preventing morbidity and mortality in acute iron poisoning has not been tested. OBJECTIVE: To determine whether deferiprone can reduce the mortality of rats following toxic oral doses of iron. METHODS: Rats were administered 612 mg/kg elemental iron by gavage, corresponding to the LD58. A parallel group received the same oral dose of iron followed by deferiprone intraperitoneally at 400 mg/kg (loading dose), followed by additional intraperitoneal injections of 200 mg/kg, 100 mg/kg and 100 mg/kg of deferiprone at one hour intervals. RESULTS: Coadministering deferiprone with the iron decreased mortality from 58% (11/19) to 15% (3/20) (p = 0.013). The administration of deferiprone was associated with urinary excretion of iron (which did not occur with iron alone) and the production of the red deferiprone-iron complex. On histological examination there appeared to be less iron in the liver and gastrointestinal tract. CONCLUSION: The coadministration of deferiprone can decrease morbidity and mortality caused by acute iron overdose. Deferiprone holds promise for the treatment of iron poisoning but additional study is required.

Primary sclerosing cholangitis in 32 children: clinical, laboratory, and radiographic features, with survival analysis.

The clinical presentation and outcome of 32 children with primary sclerosing cholangitis (PSC) are reviewed, the largest North American series. The majority of patients were diagnosed in their second decade (median age: 13 years). Four children presented before the age of 2 years, but none in the neonatal period. Seventeen patients had inflammatory bowel disease (IBD), all with colitis, 14 ulcerative colitis, and 3 Crohn's disease. Eight patients presented with chronic liver disease before clinical onset of IBD. Only 8 of 32 patients were jaundiced at presentation. Fifteen of 32 had a normal serum alkaline phosphatase (ALP) level at presentation. Nine children presented with features similar to those of autoimmune hepatitis. Cholangiography was performed in all cases and classified by a scoring system specifically developed for pediatric patients. Intrahepatic disease predominated; in only three cases a common bile duct stricture was identified requiring stenting. Findings on the initial liver biopsy were classified according to Ludwig's criteria for staging PSC: there were 15 biopsies in stages 1 to 2 and 17 biopsies stages 3 to 4. HLA class I and II antigens were determined in 27 patients. An increased incidence of HLA B8 and DR2(15) but not DRw52a (DRB3*0101) was found. Anti-neutrophil cytoplasmic antibody (ANCA) was positive in 10 of 24 patients tested. Survival analysis indicated that a later age at presentation, splenomegaly, and prolonged prothrombin time (PT) at presentation were significant contributors to the prediction of poor outcome (i.e., death or listing for transplantation). Liver transplantation was successfully performed in seven children. Physicians must maintain a high index of suspicion of PSC in any child or young adult presenting with chronic liver disease, especially in the presence of IBD, even with a normal serum alkaline phosphatase level.

Post-tonsillectomy infiltration with bupivacaine reduces immediate postoperative pain in children.

Pain management after tonsillectomy in children remains a dilemma for the anaesthetist. A previous study demonstrated that the administration of lidocaine 1% topical spray to the peritonsillar fossae before tracheal extubation provided considerable immediate postoperative pain relief in infants and children. However, the pain relief was of short duration. We were hopeful that the use of bupivacaine would offer more prolonged pain relief because of its pharmacological characteristics. Therefore, this study was designed to compare the effects of bupivacaine 0.5% with 1:200,000 epinephrine administered after tonsillectomy either as topical spray or submucosal infiltration on postoperative pain in children. Forty-three patients aged two to ten years were randomized into three groups after tonsillectomy was performed. Group (1) received 0.5 ml.kg-1 normal saline spray; (2) received 2 mg.kg-1 bupivacaine 0.5% with 1:200,000 epinephrine peritonsillar infiltration in a similar volume to Group 1 and; (3) received 2 mg.kg-1 bupivacaine 0.5% with 1:200,000 epinephrine spray to both tonsillar beds. The patients in each group were compared postoperatively with regard to the quality of pain control using the Objective Pain Score, and their analgesic requirements. Peritonsillar infiltration of bupivacaine provided superior immediate postoperative analgesia as reflected by lower recovery room pain scores (P < 0.05) and opioid requirements (P < 0.01). Ward pain scores and analgesic requirements were similar among groups. Peritonsillar infiltration of bupivacaine 0.5% with 1:200,000 epinephrine provides better post-tonsillectomy pain control in the immediate postoperative period than bupivacaine spray or placebo.

Hypercarotenemia and transaminitis in female adolescents with eating disorders: a prospective, controlled study.

PURPOSE: Hypercarotenemia and transaminitis are reported as laboratory features of anorexia nervosa. However, the specificity and sensitivity of an elevation in serum carotene and transaminase are not known. Therefore, a prospective study was undertaken to determine the clinical utility of these serum markers. METHODS: Serum carotene was measured in 46 female adolescents between 13 years and 18 years of age (21 anorexia nervosa, 17 bulimia nervosa, 8 unclassified eating disorders). Findings were compared to levels of carotene in serum samples obtained from similarly aged females with either chronic inflammatory bowel disease (22 Crohn disease, 11 ulcerative colitis) or acute medical symptoms not associated with undernutrition or intestinal inflammation (N = 26), and 21 children of either sex with dyspeptic symptoms. RESULTS: Serum carotene was elevated in 6/46 (13.0%) females with eating disorders compared with only 2/80 (2.5%) children in the three comparison groups (p < 0.01). Hypercarotenemia was present in 4/21 girls with anorexia nervosa compared with 0/17 females with bulimia nervosa (p = 0.11). Transaminitis was present in 38.5% (AST) and 7.7% (ALT) of eating disorder patients. Liver enzyme abnormalities, however, did not correlate with hypercarotenemia. Transaminitis was also not specific for eating disorders since transaminitis was observed with comparable frequency in the three comparison groups. CONCLUSIONS: These findings confirm that hypercarotenemia is a laboratory feature in some subjects with eating disorders, in particular, anorexia nervosa. The low sensitivity (13.0%) does not provide justification for its use as a screening test. However, in complicated diagnostic settings a serum carotene determination could prove useful because the specificity (97.5%), positive predictive value (75.0%), and negative predictive value (66.1%) of an elevated carotene were high. These data also show that elevated carotene levels are not associated with hepatic abnormalities. Although transaminitis is reported as a laboratory feature of eating disorders, the prevalence of such abnormalities in this study was not higher than in age-matched comparison groups.

Cardiac contusion and creatine kinase-MB: a pertinent case history and brief review of the utility of CK-MB.

Cardiac contusion is defined as the myocardial cellular damage that can result from nonpenetrating chest trauma. However the noninvasive diagnosis of this lesion is problematic. Among the criteria suggested for the diagnosis of cardiac contusion is an elevation of serum levels of the heart-specific isoform of the enzyme creatine kinase (CK-MB). We present here the case of a patient who, on the basis of an initial elevation of CK-MB, was suspected of having cardiac contusion as a result of a motor vehicle accident. The patient was clinically stable and there were no other signs to support this diagnosis. Serial analyses showed a fall in total CK to below the upper limit of the reference interval but, as a percent of total activity, CK-MB was constantly slightly elevated (values 5.1-6.5%, upper limit of normal = 4%). At the same time the patient appeared to be improving clinically. The patient's status deteriorated suddenly and he eventually went to surgery where a large intramural haematoma and a left ventricular aneurysm were discovered. The significance of the elevations of serum CK-MB is discussed and a brief review of the literature is presented.

Determination of bupivacaine in plasma by high-performance liquid chromatography. Levels after scalp infiltration in children.

The local anaesthetic bupivacaine could be very useful for analgesia in pediatric neurosurgery. Since systemic toxic reactions to bupivacaine are correlated with high plasma levels it was important, as an adjunct to clinical evaluation, to measure plasma bupivacaine. This report describes a high-performance liquid chromatography (HPLC) method for the quantitation of plasma bupivacaine. Sample preparation involves extraction into ether followed by back-extraction into HCl. After evaporation, the acid extract is redissolved and separated by reversed-phase chromatography. The assay is linear to 5 mg bupivacaine/L and shows excellent recovery and precision. With samples from children undergoing brain surgery following scalp infiltration with either 0.125% or 0.25% bupivacaine, plasma levels peak within 10 min, then fall rapidly to a plateau by 30 min. This plateau is maintained for at least 120 min. In no case did we find supposed toxic levels of bupivacaine.

Relationship between the pharmacokinetics and iron excretion pharmacodynamics of the new oral iron chelator 1,2-dimethyl-3-hydroxypyrid-4-one in patients with thalassemia.

Single-dose and steady-state pharmacokinetics of the new oral iron chelator, 1,2-dimethyl-3-hydroxypyrid-4-one (L1) were studied in 14 patients with thalassemia and correlated with iron excretion. Food prolongs the rate of absorption of L1, but it does not affect significantly the extent of absorption measured by the area under the plasma concentration-time curve. Similarly, it does not affect the chelation potential of the drug. The mean elimination half-life of the drug is 3 hours, suggesting that a divided dose every 8 hours may assure better chelation. Our steady-state studies reveal that urinary iron excretion is independently influenced by body iron load (measured by ferritin levels) and by steady-state trough concentrations of the drug. While patients were receiving an unchanged regimen of 75 mg/kg/day, we have detected a gradual and significant decrease in trough concentrations in the presence of unchanged patients' compliance monitored by the Medication Event Monitoring System, diaries, and pill count. These findings suggest self-induction of L1 metabolism or decreased absorption during long-term therapy. Because of the concentration-dependent iron excretion, patients may need increasing doses to achieve negative iron balance.

Scalp infiltration with bupivacaine in pediatric brain surgery.

To evaluate whether local anesthetic scalp infiltration blunts hemodynamic responses to craniotomy in anesthetized children (age, 2-18 yr), two concentrations of bupivacaine (0.125% and 0.25%) with vasoconstrictor (epinephrine 1:400,000) were compared with control data when a solution of vasoconstrictor alone was injected. Arterial plasma levels of bupivacaine were measured by high-pressure liquid chromatography. Statistically significant increases in mean arterial pressure and heart rate above baseline measurements occurred in the control group during the period between scalp incision and dural reflection (P less than 0.05). Both concentrations of bupivacaine prevented these increases. Mean arterial pressure and heart rate during scalp incision and scalp reflection were significantly higher in the control group than in both bupivacaine groups (P less than 0.05). Peak bupivacaine plasma levels (mean +/- SD) occurred either 5 or 10 min after infiltration and were significantly higher in the 0.25% group (0.48 +/- 0.31 microgram/mL) than the 0.125% group (0.14 +/- 0.13 microgram/mL) (P less than 0.05). These results suggest that bupivacaine infiltration blocks the hemodynamic response to craniotomy. A concentration of 0.125% bupivacaine with 1:400,000 epinephrine is as effective as 0.25% bupivacaine with 1:400,000 epinephrine at reducing the hemodynamic response to craniotomy. Because the lower concentration of bupivacaine produces lower blood levels, we recommend 0.125% bupivacaine with 1:400,000 epinephrine as a useful, safe adjunct to general anesthesia in children undergoing craniotomy.

Coffee and alcohol as determinants of risk of pancreas cancer: a case-control study from Toronto.

Results are reported from a population-based study of 249 cases of pancreas cancer and 505 controls carried out in Toronto, Canada, between 1983 and 1986. Lifetime consumption of coffee and alcohol and medical histories were assessed by personal interviews. No evidence of any association was found with different types of coffee or alcohol after adjusting for smoking, calories and fibre intake. There was a significant increased risk associated with a history of diabetes mellitus within 5 years of cancer development. A protective effect of a history of some allergic conditions, hay fever, eczema and asthma, was observed, although the relative risks were not significant (p value greater than 0.10).

Comparison of oral iron chelator L1 and desferrioxamine in iron-loaded patients.

The efficacy of the oral iron chelator 1,2-dimethyl-3-hydroxypyrid-4-one (L1) was compared with that of subcutaneous desferrioxamine in 26 patients with transfusional iron overload. Immediately after red-cell transfusion, 20 patients were randomised to receive either desferrioxamine (50 mg/kg daily as a 12 h subcutaneous infusion), or L1 (50 mg/kg daily by mouth). Patients were evaluated during treatment with the other drug after transfusion the next month. Mean (SD) daily urinary iron excretion was lower during L1 than during desferrioxamine (12.3 [6.7] vs 18.2 [15.3] mg/day). In 5 patients the dose of L1 was raised from 50 to 75 mg/kg daily; mean urinary iron excretion rose from 13.8 (7.0) mg/day to 26.7 (17.8) mg/day, comparable with that during desferrioxamine (24.9 [24.3] mg/day). Faecal iron excretion rose slightly over baseline in 6 patients studied during L1 administration (from 8.5 [0.9] mg/day to 12.2 [0.9] mg/day). Pharmacokinetic studies showed an elimination half-life for L1 of 117-237 min. Studies in dogs and in volunteers showed no absorption of the L1-iron complex, excluding a contribution of absorption of intraluminal complexes of L1 and food iron to urinary iron excretion. Further animal toxicity testing is needed before L1 can be studied in a broader group of patients.