Determination of ionised calcium by ion selective electrode is not independent of albumin concentration

The relationship of ionised calcium measurement to changes in serum total protein and albumin were studied both in vivo and in vitro. During venostasis serum ionised calcium was determined in 10 control subjects using an Orion SS20 analyser. A slight but significant increase in ionised calcium occurred only after prolonged venostasis (15 min), when gross changes in total protein and albumin were seen. The effect of albumin concentration on serum ionised calcium was studied in vitro by the dialysis technique of Payne. The increase in ionised calcium in 40 sera was 0.0198 mmol/l per 10 g albumin change. We conclude that albumin-related variation in serum ionised calcium determination required such gross changes that correction is rarely necessary in clinical practice. When gross albumin alteration occurs, the appropriate correction for the analyser used should be determined and applied.     

Determination of serum ionised calcium by ion-exchange electrode in normal subjects

Serum ionised calcium concentration [Ca2+] was measured with a calcium selective electrode in 65 normal people. A mean value of 1.06 mmol/l (+/- 0.04 S.D.) with an actual range of 0.97 to 1.13 mmol/l was obtained. Serum samples refrigerated at 4 degrees C for 24 h were satisfactory for analysis. Storage of whole blood samples for 6 h at room temperature before separation caused a very small error (+0.04 mmol/l). Mean results and ranges were similar in males and females and there was no significant correlation with age. No significant change in serum [Ca2+] was found following a normal meal. Serum [Ca2+] and total serum calcium showed a very slight correlation (r = 0.35). The method is reproducible and sensitive.     

Detection of citrate overdose in critically ill patients on citrate-anticoagulated venovenous haemofiltration: use of ionised and total/ionised calcium.

BACKGROUND: The objective of this study was to elucidate the most practical and effective laboratory measurement for monitoring citrate in critically ill patients undergoing citrate-anticoagulated continuous venovenous haemofiltration (CVVH). METHODS: This observational study was performed at the mixed medical and surgical intensive care unit of a regional teaching hospital. The study population comprised ten consecutive critically ill patients with acute renal failure and indication for haemofiltration with the use of regional anticoagulation with citrate. Serum samples for the measurement of citrate and total and ionised calcium were taken from the pre- and post-filter compartments and from the arterial circulation of patients during citrate-anticoagulated CVVH. RESULTS: Receiver operating characteristic (ROC) curve analysis showed that for detecting citrate overdose (defined as a citrate concentration >1.0 mmol/L) the best cut-off limits for total/ionised calcium and ionised calcium were 2.1 and 0.8 mmol/L, respectively. Sensitivity and specificity for the cut-off limit of 2.1 for total/ionised calcium were 89% and 100%, and 84% and 100%, respectively, for the cut-off limit of 0.8 mmol/L for ionised calcium. CONCLUSIONS: In patients without liver insufficiency, total/ionised calcium performed slightly better than ionised calcium in detecting elevated citrate concentrations. However, because of the simplicity of its measurement, ionised calcium is preferred. Measurement of citrate is not necessary.     

Effect of heparin concentration and infusion rate on the patency of arterial catheters

In a prospective randomized controlled trial involving 470 arterial catheters in 470 children, we studied the effect of changing either the concentration or the flow rate of a heparin infusion. Although catheters tended to remain patent longer with a flow rate of 2 ml/h rather than 1 ml/h, the difference was not statistically significant. Increasing the heparin concentration from 1 to 5 U/ml significantly prolonged catheter patency.     

Effect of hematocrit and added heparin on ionized calcium in capillary blood samples from neonates

Sampling of capillary blood for determination of ionized calcium (Ca2+) in neonates requires that extra heparin be added to prevent clotting in the sampling tube and (or) in the Ca2+ analyzer. Because the additive dissolves in the plasma compartment, different hematocrit (erythrocyte volume fraction, EVF) values may cause different results for Ca2+. To study the effect of EVF and heparin additive, we repeatedly removed plasma, thereby increasing the EVF. These samples with different EVF's were aspirated into commercial capillary tubes containing heparin and, according to our routine procedure, an additional 10 microL (approximately 0.9 int. unit) of sodium heparin. We found a negative bias of 0.05-0.09 mmol/L in Ca2+, depending on the EVF. Adding saline instead of heparin gave the same effect, indicating that this bias was entirely due to dilution. We suggest compensating for this by adding 0.09 mmol/L to the actual value for ionized calcium when EVF exceeds 70%. The increase in Ca2+ in neonates on days 1 to 5 postpartum is physiological and not an effect of change in EVF.     

Response of Plasma Histaminase Activity to Small Doses of Heparin in Normal Subjects and Patients with Hyperlipoproteinemia

The release of histaminase activity in plasma after small intravenous of heparin was studied in 85 normal subjects and patients. In normal subjects, plasma histaminase activity (basal level, 1.7+/-0.1 U/ml, mean +/-SEM) increased 1.6+/-0.2 U/ml after 10 U of heparin/kg, 8.5+/-2.4 U/ml after 20 U/kg, and 33+/-4.9 U/ml after 75 U/kg. The extent of the increase varied widely among individuals but in a particular individual the response was constant and dose-dependent. Histaminase activity rose to peak levels within 7-15 min and then declined exponentially with a half-life of 40-120 min. This pattern of response was also observed in two patients with the histaminase-producing tumor, medullary carcinoma of the thyroid. A significantly reduced response was observed, however, in 14 patients with type I hyperlipoproteinemia, a disorder in which high plasma triglyceride levels are associated with low postheparin plasma lipolytic activity. After 10 U heparin/kg, plasma histamine activity increased 0.5+/-0.2 U/ml, and after 75 U heparin/kg, 10.9+/-5.6 U/ml. In contrast, in 27 patients with other types of hyperlipoproteinemia in whom postheparin lipolytic activity was normal, the increase (2.4+/-0.6 U/ml) in plasma histaminase activity after 10 U heparin/kg was not significantly different from that of normal subjects. The reduced response of the plasma histaminase activity to heparin in patients with type I hyperlipoproteinemia did not appear to be due to the presence of lipemia or to an inhibitor of the enzyme in plasma. These findings suggest that many patients with type I hyperlipoproteinemia may have deficient release of both lipolytic and histaminase activities into plasma after heparin administration.     

糖尿病肾病患者血液透析股静脉置管肝素封管浓度的探讨

目的　探讨糖尿病肾病股静脉置管肝素稀释封管的效果。方法　将 75例糖尿病肾病血液透析患者随机分成3组 ,每组 2 5例 ,实验Ⅰ组用 4ml肝素盐水 (5 0 0U/ml)封管 ,实验Ⅱ组用 4ml肝素盐水 (15 0 0U/ml)封管 ,对照组用 4ml肝素盐水 (2 5 0 0U/ml)封管 ,比较 3组的堵管、局部渗漏发生率 ,凝血酶原时间 (PT)及凝血酶时间 (TT)。结果　实验Ⅰ组肝素封管液堵塞的发生率与其他两组相比有显著差异 (P <0 .0 5 ) ,实验组间PT及TT值无明显差异 (P >0 .0 5 ) ,对照组局部渗漏的发生率明显高于实验组 (P <0 .0 1)。结论　糖尿病肾病血透股静脉置管使用4ml肝素盐水 (15 0 0U/ml)封管较安全可靠     

Inhibitory Effect of Heparin on Gentamicin Concentrations in Blood

In monitoring gentamicin concentrations in the blood of patients with renal insufficiency, the assayed antibiotic concentration was found to be lower when the sample was drawn as heparinized plasma rather than as serum. This lowering of gentamicin concentrations by heparin was studied further by adding increasing doses of heparin and various amounts of gentamicin to human serum. With a range of 2 to 100 units of heparin per ml, gentamicin concentrations in the serum were lowered by 9 to 14%; with higher heparin concentrations, an even greater and increasing inhibition was noticed, reaching 56% for 1,000 units/ml. This inhibitory effect of heparin on gentamicin was reversible by dilution, indicating that it was not due to degradation or to formation of an inactive chemical complex. Underestimation by the laboratory of gentamicin concentrations in blood is likely to be greatest with capillary tubes, with which the concentration of heparin is especially high. With clinical heparinization, the amount of active heparin in the blood does not exceed 10 units/ml and is for the most part under 3 units/ml; thus, therapeutically significant inhibition of the antibiotic is unlikely in patients receiving anticoagulation.     

The calcium ion activity and the standardized excretion rate of calcium in urine of healthy adults

A standardized protocol is described for the study of the calcium excretion in urine. After 12 h of fasting, urine is collected during 4 h with a water load of 10 ml per kg body weight. Urine is also collected during the following 20 h period on the habitual water and calcium intake. Reference values for 48 healthy adults are given as 0.25 and 0.75 quantiles. The measured activity of calcium ions (Ca2+) in urine is 0.09-0.27 mmol/kg for the 4 h period, 0.34 to 0.52 mmol/kg for the 20 h period; pH values are 5.61-6.43 (4 h) and 5.46 to 6.04 (20 h). The concentrations of total calcium are 0.67-2.05 mmol/l (4 h) and 3.16 to 4.94 mmol/l (20 h). The value for the excretion rate of calcium (standardized to a creatinine clearance of 100 ml/min) is 1.30-3.24 mumol/min for the 4 h period and 3.06-4.88 mumol/min for the 20 h period, with no significant difference between the results for men and women. The relationship between the Ca2+ activity and pH was studied in urine titrated with HC1 or NaOH. In all urine the Ca2+ activity falls with increasing pH in a typical biphasic manner. This indicates the need for simultaneous measurement of the pH in order to interpret data for the Ca2+ activity in urine.     

Changes in plasma ionised calcium within 24 hours of trauma in patients infused with the calcium containing colloid Haemaccel during fluid resuscitation.

OBJECTIVE: To determine the changes in ionised plasma calcium levels over a 24 h period in patients sustaining blunt trauma injuries and infused with the calcium containing colloid Haemaccel (6.25 mmol/ litre Ca2+). METHODS: The study was carried out on 24 trauma patients who attended the accident and emergency (A&E) department of the Leicester Royal Infirmary and required fluid resuscitation. Nineteen patients, with a mean injury severity score (ISS) of 14 (range 6 to 36), were given an infusion of Haemaccel; five patients in the control group with an ISS of 12 (range 6 to 19) were infused non-calcium-containing crystalloid. All types of fluids were recorded and serial plasma ionised calcium values were measured over a 24 h period. RESULTS: The mean pre-Haemaccel ionised calcium value fell to 0.71 mmol/litre following trauma. The mean values (mmol/litre) obtained in patients infused with Haemaccel were measured at 2, 4, 8, and 24 h. In the Haemaccel group these values were 1.38 (SD 0.34), 1.40 (0.44), 1.23 (0.27), and 1.18 (0.31) (at least P < 0.001 v baseline). The rise in calcium at 2 h was proportional to the volume of Haemaccel infused (r = 0.917; P < < 0.001). CONCLUSIONS: In all patients the plasma ionised calcium rose on infusion of Haemaccel and in a least one measurement 50% of patients developed hypercalcaemia (Ca2+ < 1.30 mmol/litre). The clinical significance of this is at present unclear.     

肾移植术后股静脉置管肝素封管液浓度的探讨

目的 探讨肾移植患股静脉置管用稀释肝素封管的效果。方法 将90例肾移植患随机分成3组，每组30例，试验I组用10ml肝素盐水（50U／ml)封管，试验组Ⅱ组用10ml肝素盐水（25U/ml）封管，对照组用10ml肝素盐水（125U／ml) 封管，对堵管，局部渗漏的发生率，凝血酶原时间（PT）及凝血酶时间（TT）进行比较。结果 3组肝素封管液堵管的发生率无显差异，试验组间PT及TT值无明显差异，与对照组有显差异（P＜0．05），试验组与对照组局部渗漏的发生率有显差异（P＜0．01）。对照组明显高于试验组。结论 肾移植术后患股静脉置管使用10ml肝素盐水（每10ml含肝素25U）封管较安全可靠。     

Release of somatostatin-like immunoreactivity from the perfused canine thyroid. Selective stimulatory effect of calcium ions.

It is well accepted that the C cells of the thyroid contain somatostatin, but the role in local endocrine function has not yet been firmly established in this organ, and it has not been proved that thyroidal somatostatin is released into the circulation. We have measured the contents of somatostatin-like immunoreactivity in the effluent of canine thyroid glands perfused without recirculation with a synthetic buffer medium. During basal conditions a definite release was consistently found in the order of 10 pg/ml corresponding to 12 pg/min. The somatostatin-like immunoreactivity was studied in dilution experiments and by gel-filtration chromatography, and found to have properties identical to those of synthetic cyclic somatostatin, which was also recovered quantitatively when added to sampling tubes. Various compounds were infused in concentrations that are highly active in pancreas perfusion experiments. 14-min infusion of arginine, 5 and 11.5 mmol/liter; isoproterenol, 10 and 23.7 nmol/liter and 68.7 mumol/liter; acetylcholine, 5 mumol/liter, carbamylcholine, 10 and 100 mumol/liter; glucagon, 1 and 30 nmol/liter; and porcine calcitonin, 1 and 100 ng/ml did not affect the basal release of somatostatin-like immunoreactivity significantly. Neither did an increase from the control level of 4 mmol/liter glucose of 10 or 20 mmol/liter, nor an increase in the control level of 4.4 mmol/liter K+ to 7.5 or 14.4 mmol/liter. Each of these compounds were tested in three or four dogs. The effect of an increase in Ca++ from the control level of 1.5 mmol/liter to 2.25, 3.0, and 4.5 mmol/liter was tested in random order in five thyroid lobes. All three doses elicited an immediate increase in effluent somatostatin-like immunoreactivity. In most experiments the response was biphasic with an early spike, followed by a stable level that was maintained during prolonged Ca++ infusion. The secretory response was not diminished through a series of repeated short pulses of calcium infusion. The response to 3.0 mmol/liter Ca++ (control period 8.4 +/- 1.5, test period 337 +/- 110 pg/ml, mean +/- SE) and 4.5 mmol/liter Ca++ (control period 9.5 +/- 1.4, test period 386 +/- 125) were significantly higher than 2.25 mmol/liter Ca++ (control period 7.2 +/- 1.0 test period 140 +/- 39), while there was no significant difference between responses to the two high doses. Infusion of salmon calcitonin, 10 ng/ml and 1 microgram/ml; or porcine calcitonin, 1 microgram/ml during calcium stimulation (2.25 mmol/liter of Ca++) did not induce alterations in the release of somatostatin-like immunoreactivity. The results demonstrate that thyroidal somatostatin is mobilizable, and it appears to be selectively sensitive to calcium stimulation, indicating a possible role in calcitonin release control.     

Effect of increasing doses of magnesium in experimental pulmonary hypertension after acute pulmonary embolism

Objective To investigate the dose-related effects of magnesium on pulmonary vascular resistance and associated changes in cardiac output in porcine micro-embolic pulmonary hypertension.Design Prospective, interventional animal study.Setting University animal laboratory.Subjects Forty anaesthetised and ventilated piglets.Interventions Right heart catheterisation for the measurement of cardiac output, pulmonary artery pressure, central venous pressure and pulmonary capillary wedge pressure; arterial cannulation for measurement of arterial pressures and ionised magnesium levels; calculation of pulmonary and systemic vascular resistance before and after induction of acute pulmonary micro-embolism, and without or with the administration of magnesium (0.5, 1.0, 2.0 mmol/kg bolus and 1 mmol/kg bolus followed by 1 mmol/kg per h continuous infusion).Measurements and main results The bolus administration of increasing doses of magnesium (0.5, 1.0, 2.0 mmol/kg) was associated with an increase in ionised serum magnesium levels and a dose-dependent decrease of mean pulmonary arterial pressure, an increase of cardiac output and a decrease of pulmonary vascular resistance. This effect was sustained after bolus administration (1 mmol/kg) followed by a continuous infusion of magnesium (1 mmol/kg per h).Conclusions Magnesium has a directly dose-dependent beneficial effect on the circulation in acute embolic pulmonary hypertension and improves cardiocirculatory impairment in massive pulmonary embolism (PE).     

两种不同封管方式用于植入式静脉输液港的观察研究

目的 比较使用植入式静脉输液港的肿瘤患者在输液后和输液周期结束拔针时分别使用生理盐水或肝素钠封管的效果,推荐合适的封管方式。方法 将120例植入式静脉输液港的肿瘤患者随机分为观察组和对照组,各60例。观察组每天输液后采用10ml肝素钠生理盐水（100U/ml）脉冲式正压封管,1个输液周期结束拔针时先用10ml生理盐水脉冲式冲管后再用5ml肝素钠生理盐水（100U/ml）正压封管。对照组每天输液后采用10ml生理盐水脉冲式正压封管,1个输液周期结束拔针时用10ml生理盐水脉冲式正压封管。观察两组患者静脉输液港的堵管发生情况。结果 在每次输液后和输液周期结束拔针时使用生理盐水和肝素钠封管效果差异无统计学意义（P>0.05）结论：对于静脉输液港的封管方法,建议使用生理盐水封管,因其安全性、有效性、经济性、可操作性强的优点,值得推广应用。     

6项临床化学指标适用血浆样本类型的研究

目的 研究不饱和铁结合力（UIBC）、β-羟丁酸（β-HB）、肌红蛋白（MYO）、丙氨酸氨基转移酶（ALT）、铁（Fe）和磷（P）试剂盒可接受的血浆样本类型.方法 使用血清、肝素血浆和EDTA血浆采血管,收集研究对象静脉血样本.样本离心处理后,在BS-800全自动生化分析仪上,分别检测血清和血浆样本中UIBC,β HB,MYO,ALT,Fe和P的水平,并对血清和血浆样本结果进行统计学分析.结果 血清样本组UIBC,β HB,MYO测定结果（34.4±9.8 μmol/L,0.41±0.92mmol/L和48.0±21.6 ng/ml）与肝素血浆样本组（34.6±10.2 μmol/L,0.41±0.92 mmol/L和46.7±20.1 ng/ml）比较差异无统计学意义（t=0.77, 0.88和1.33,P均＞0.05）,血清样本组MYO测定结果（113.2±118.0 ng/ml）和EDTA血浆样本组（113.0±116.3 ng/ml）比较差异无统计学意义（t=0.25,P＞0.05）.血清样本组ALT,Fe和P测定结果（76.9±155.7 U/L,17.7±16.3 μmol/L和1.14±0.15 mmol/L）与肝素血浆样本组（76.3±155.8 U/L,17.9±16.3 μmol/L和1.11±0.15 mmol/L）比较差异有统计学意义（t=2.99,-2.25和5.61,P均＜0.05）,血清样本组P测定结果（1.14±0.15mmol/L）和EDTA血浆样本组（1.09±0.14 mmol/L）比较差异有统计学意义（t=13.46,P＜0.05）.但血清和肝素血浆ALT,Fe和P测定结果,及血清和EDTA血浆P测定结果均呈正相关（相关系数分别为0.999 9,0.999 0,0.987 5和0.9936,P均＜0.01）,在医学决定水平处的偏差（4.2％-3.2％）均小于允许误差的50％.结论 肝素血浆样本类型适用于UIBC,β HB,MYO,ALT,Fe和P试剂盒的测定,EDTA血浆样本类型适用于MYO和P的测定.     

三种封管液对小儿留置针的影响比较

目的探讨三种封管液对小儿留置针留置效果的影响。方法选择需静脉留置套管针输液的患儿100例,随机分为1、2、3三组,分别采用50 U/ml的肝素钠盐水、10 U/ml的肝素钠盐水和生理盐水作为封管液,对三组留置针的留置时间、静脉炎和堵管发生率进行比较。结果 1组的留置时间明显优于2、3组(P0.05),三组之间静脉炎和堵管发生率的比较无统计学意义(P0.05)。结论 50 U/ml肝素盐水封管效果优于10 U/ml肝素盐水和生理盐水。     

Effect of Propofol With and Without EDTA on Haemodynamics and Calcium and Magnesium Homeostasis During and After Cardiac Surgery

Objective: To determine the effect of the addition of disodium edetate (EDTA) to propofol on haemodynamics, ionised calcium and magnesium serum concentrations, and adverse events during cardiac surgery. Design: Double-blind, randomised, multicenter trial. Setting: Operating room and intensive care unit of 5 academic health centres. Patients: A total of 102 evaluable patients, aged 34 to 85 years, undergoing first-time, elective coronary artery bypass graft surgery. Interventions: Comparison of propofol with EDTA and propofol without EDTA, each in conjunction with the opioid sufentanil, for intraoperative anaesthesia and postoperative sedation. Measurements and Results: There were no significant differences at any time between the two formulations in any clinical chemistry measurements, including ionised calcium, ionised magnesium, total calcium, parathyroid hormone, blood urea nitrogen, creatinine, sodium, potassium, and phosphate. During bypass, the mean concentration of ionised calcium decreased to below the normal range, but the decrease was similar in both groups (propofol with EDTA, 0.98 - 0.07 mmol/L [N = 51]; propofol, 0.99 - 0.10 mmol/L [N = 51]; p = NS). Calcium concentration returned to normal after rewarming. Mean ionised magnesium concentrations remained within normal limits in both groups. Similarly, there were no clinically meaningful differences between treatments with respect to haemodynamic variables, efficacy variables, or incidence of adverse events. Conclusions: The inclusion of EDTA in the current formulation of propofol appears to have no significant effects on calcium and magnesium profiles, renal function, haemodynamic variables, or other indicators of safety and efficacy during intraoperative anaesthesia and postoperative sedation in patients undergoing cardiac surgery.     

The effects of heparin anticoagulants and fill volume in blood gas syringes on ionized calcium and magnesium measurements

We studied the effects of several heparin anticoagulants on ionized calcium and ionized magnesium measurements. Venous blood from 24 healthy donors was drawn into 20-ml syringes without an anticoagulant, and immediately analyzed for control results. They were then transferred to completely fill and half-fill each of four brands of syringes, and an evacuated non-anticoagulated blood-collection tube. All were analyzed for ionized calcium and magnesium. In some cases, either saline or a Ca/Mg solution was added to increase the range of concentrations. The final concentrations ranged from 0.94 to 2.09 (ionized calcium) and from 0.41 to 1.06 mmol/l (ionized magnesium). In full syringes, mean changes in ionized calcium or magnesium were <0.01 mmol/l over a range of concentrations usually encountered. The only definite effect was noted in half-full Martell syringes, where ionized calcium was lower by 0.028 mmol/l. At very high ionized calcium concentrations (>1.95 mmol/l) and ionized magnesium concentrations (>0.95 mmol/l), a few changes were noted of little clinical significance. We conclude that all the syringes evaluated have no clinically significant effects on ionized calcium or ionized magnesium concentrations when filled to capacity. When half-full, a few changes of marginal clinical significance were noted. All these effects were less than observed in serum, which is apparently affected by sample processing and/or clotting.     

Binding of glycosaminoglycans to sodium urate and uric acid crystals

The binding of heparin, chondroitin sulphate and the low molecular weight heparin analogue pentosan polysulphate to sodium urate and uric acid crystals was studied by the use of radioactively labelled glycosaminoglycans were used in the binding step, and varying amounts of unlabelled glycosaminoglycans for the competition experiments. The experiments were carried out in 140 mmol/l NaCl at pH 6, with or without 5 mmol/l CaCl2 in the solution. A reversible and almost complete binding of heparin and chondroitin sulphate to sodium urate crystals did occur in the presence of calcium, whereas pentosan polysulphate bound incompletely. The binding was much less pronounced in the calcium-free conditions. Uric acid crystals did not bind any of the three inhibitors, not even with calcium present. The clinical relevance depends on whether sodium urate microcrystals are present in the urine of calcium stone patients, to cause a binding and thereby a masking or inactivation of these inhibitors in the urine, which seems to be possible in the presence of calcium. However, the potential of pentosan polysulphate for the treatment of calcium stone patients does not seem to be at risk from this effect.     

Errors due to heparin in the estimation of plasma sodium and potassium concentrations

The effect of adding sodium heparin (5000 U/ml and 1000 U/ml) to whole blood on the concentrations of plasma sodium and potassium was examined. When the analysis was done by flame photometry both preparations of heparin caused an increase in plasma sodium concentration. If the analysis was done by a direct ion selective electrode method the 5000 U/ml heparin caused a decrease and the 1000 U/ml caused an increase in plasma sodium concentration. Plasma potassium concentration decreased when 1000 U/ml heparin was added irrespective of the method of analysis. It is recommended that sodium heparin should not be used in samples taken for estimation of sodium and potassium.