Effect of high doses of sodium bicarbonate in acute organophosphorous pesticide poisoning. Alkalinization of intracuff lidocaine: efficacy and safety. Rapid infusion of sodium bicarbonate and albumin into high-risk premature infants soon after birth: a controlled, prospective trial. Efficacy of alkalinized lidocaine for reducing pain on intravenous and epidural catheterization. Increasing blood flow increases kt/V(urea) and potassium removal but fails to improve phosphate removal. Intrahepatic arterial versus intravenous fluorouracil and folinic acid for colorectal cancer liver metastases: a multicentre randomised trial. Hyperbaric or normobaric oxygen for acute carbon monoxide poisoning: a randomised controlled clinical trial. Intraoperative antifibrinolysis and blood-saving techniques in cardiac surgery. Prospective trial of 3 antifibrinolytic drugs. Comparison of 1 alpha-OH-vitamin D3 and high doses of calcium carbonate for the control of hyperparathyroidism and hyperaluminemia in patients on maintenance dialysis.
The sodium bicarbonate (NaHCO3) dosage used in treating the patients with organophosphorous pesticide (OP) poisoning did not result in sufficient alkalinization of the blood. We thus investigated the effects of higher doses by infusion (5 mEq/kg over 1 hour, followed by 5-6 mEq/kg daily until recovery or death) to maintain the arterial pH between 7.45 and 7.55. There were 26 (14 M and 12 F) patients aged 24.1 +/- 9.7 years and 27 (16 M and 11 F) aged 25.7 +/- 9.1 years in the test and contro groups, respectively. Arterial blood pH of the test group (7.48 +/- 0.02) was much higher (p < 0.0001) than the controls (7.36 +/- 0.02). The total atropine doses used for the control patients (129.45 +/- 61 mg) was significantly (p = 0.048) higher than the controls (93.4 +/- 59.1 mg). Hospitalization days were statistically higher (p = 0.037) in the controls (5.59 +/- 1.97 days) than in the bicarbonate group (4.33 +/- 1.99 days). Infusion of high doses of NaHCO3 appears to be beneficial in treatment of patients with OP poisoning. When alkalinized lidocaine instead of air is used to fill the endotracheal tube (ETT) cuff, coughing, and bucking are decreased during extubation when ventilation is controlled with N2O. However, sodium bicarbonate (NaHCO3) used to transform lidocaine hydrochloride (L-HCl) to lidocaine base induces a pH increase that could be irritating for mucosa in the case of cuff rupture. Therefore, we determined, in a randomized controlled study with controlled patient ventilation without N2O, whether the smallest concentrations of NaHCO3 (1.4% versus 8.4%) reduced diffusion (in vitro evaluation) and other secondary clinical benefits. After pH determination of different solutions (2 mL of 2% L-HCl and 2 to 6 mL of 8.4%, or 1.4% NaHCO3), an in vitro lidocaine diffusion through the ETT cuffs was evaluated (2 mL of 2% L-HCl and 3 mL of 8.4% or 1.4% NaHCO3). Then, adult patients scheduled for total thyroidectomy surgery were consecutively enrolled (n = 20 for each group). The ETT cuff was filled with air (group air) or with alkalinized lidocaine (2 mL of 2% L-HCl) using 8.4% (group large dose) or 1.4% (group small dose) of NaHCO3. After tracheal extubation, sore throat was evaluated by visual analog scale as the main end-point of the study. Hoarseness, bucking, dysphonia, dysphagia, cough, restlessness, and postoperative nausea and vomiting were also evaluated. There was a slight tendency toward a slower release when a small concentration of NaHCO3 was used (i.e., 1.4%). Compared with group air, the alkalinized-lidocaine groups had a significant reduction in sore throat during the 24-h postoperative period (P < 0.0001). The difference was not significant between the two alkalinized lidocaine groups. This increase in ETT tolerance was confirmed by the analysis of secondary end-points. No laryngospasm, rupture of ETT cuff, or depression of the swallowing reflex were recorded. A decrease in sore throat during the postoperative period was recorded when the cuff was inflated with a small dose of alkalinized lidocaine (i.e., 40 mg of L-HCl and 1.4% of NaHCO3) rather than with air when ventilation was controlled without N2O. We conducted a controlled, prospective trial to evaluate the effectiveness of rapidly infusing sodium bicarbonate (NaHCO3) and salt-poor albumin into high-risk, premature infants in the first 2 hours of life. Fifty-three infants, randomized into one of four treatment groups, received 8 ml. per kilogram of a solution containing either (A) glucose in water, (B) salt-poor albumin, (C) NaHCO3, or (D) a combination of albumin and NaHCO3. After the initial infusion, the babies received no colloid or alkali solutions until 4 hours of age. We managed them supportively with warmth, appropriate oxygen administration, isotonic fluid infusion, and close monitoring. Among the infants who received alkali, 14 of 26 acquired the respiratory distress syndrome (RDS), 11 died, and four had intracranial hemorrhage. Among babies who received no alkali, RDS occurred in 11 of 27, 5 died, and none had intracranial hemorrhage. These results do not support the common practice of rapidly infusing NaHCO3 into high-risk, premature infants, and they suggest that the early management of such infants needs renewed critical evaluation. To investigate whether increasing the pH of lidocaine could reduce the pain caused by its skin infiltration as well as that caused by intravenous and epidural needle insertion.
                A randomized, double-blind trial was undertaken in patients who were allocated to receive topical anesthesia with either plain (plain group; n = 25) or alkalinized lidocaine (alkalinized group; n = 25). An alkalinized lidocaine solution was prepared by adding 8.4% sodium bicarbonate to a plain 1% lidocaine solution at a ratio of 1 : 10. Pain was assessed using the verbal analog scale (VAS).
                In the alkalinized group, the VAS scores on skin infiltration in the hand (2.5 +/- 1.4) and the back (2.7 +/- 1.4) were significantly lower than the respective scores in the plain group (3.5 +/- 1.4, and 4.9 +/- 1.9). Although the VAS score on intravenous needle insertion did not differ between the two groups, the VAS score on epidural needle insertion was significantly lower in the alkalinized group (1.3 +/- 1.0) than in the plain group (3.6 +/- 1.3).
                Alkalinization of lidocaine was effective in attenuating pain on skin infiltration and on epidural needle insertion. Hyperphosphatemia and hyperkalemia are major determinants of morbidity and mortality in hemodialysis patients. Half of the dialysis population suffers from hyperphosphatemia which is now recognized as an important cardiovascular disease risk factor. It is, therefore, necessary to improve the removal of these molecules. In this study, we investigated the effect of enhancing blood flow on Kt/V for urea (Kt/Vu), potassium and phosphate removal.
                Thirteen patients were investigated in a randomized, cross-over, prospective study using 3 blood flows (Qb) of 200,250 and 300 ml/min which gave 39 standardized high-flux hemodialysis treatments. Effective blood flows were measured by ultrasonic flow meter. Quantification of delivered dialysis dose was performed by partial dialysate and ultrafiltrate collection for the determination of potassium and phosphate removal and by blood urea concentrations for determination of Kt/Vu.
                Kt/Vu rose significantly from 1.10 +/- 0.14 to 1.22 +/- 0.14 and finally to 1.39 +/- 0.16 (p = 0.0001) with increasing Qb similar to the increase in potassium removal from 53.0 +/- 2.4 to 63.4 +/- 2.6 and to 74.2 +/- 3.8 mMol (p = 0.01). Phosphate removal only improved from 28.1 +/- 1.3 to 31.4 +/- 1.5 (p = 0.050) when Qb was increased from 200 to 250 ml/min but remained unchanged at 31.2 +/- 1.5 mMol (NS compared to phosphate removal at Qb = 250 ml/min) when Qb was increased to 300 ml/min.
                Increasing delivered Kt/Vu and potassium removal with higher Qb fails to produce the same desired effect with phosphate removal during high-flux hemodialysis. The liver is the most frequent site for metastases of colorectal cancer, which is the second largest contributor to cancer deaths in Europe. We did a randomised trial to compare an intrahepatic arterial (IHA) fluorouracil and folinic acid regimen with the standard intravenous de Gramont fluorouracil and folinic acid regimen for patients with adenocarcinoma of the colon or rectum, with metastases confined to the liver.
                We randomly allocated 290 patients from 16 centres to receive either intravenous chemotherapy (folinic acid 200 mg/m2, fluorouracil bolus 400 mg2 and 22-h infusion 600 mg/m2, day 1 and 2, repeated every 14 days), or IHA chemotherapy designed to be equitoxic (folinic acid 200 mg/m2, fluorouracil 400 mg/m2 over 15 mins and 22-h infusion 1600 mg/m2, day 1 and 2, repeated every 14 days). The primary endpoint was overall survival, and analysis was by intention to treat.
                50 (37%) patients allocated to IHA did not start their treatment, and another 39 (29%) had to stop before receiving six cycles of treatment because of catheter failure. The IHA group received a median of two cycles (0-6), compared with 8.5 (6-12) for the intravenous group. 45 (51%) IHA patients who did not start or did not receive six cycles switched to intravenous treatment. In both groups, grade 3 or 4 toxicity was uncommon. Median overall survival was 14.7 months for the IHA group and 14.8 months for the intravenous group (hazard ratio 1.04 [95% CI 0.80-1.33], log-rank test p=0.79). Similarly, there was no significant difference in progression-free survival.
                Our results showed no evidence of an advantage in progression-free survival or overall survival for the IHA group; thus continued use of this regimen cannot be recommended outside of a clinical trial. To assess neurological sequelae in patients with all grades of carbon monoxide (CO) poisoning after treatment with hyperbaric oxygen (HBO) and normobaric oxygen (NBO).
                Randomised controlled double-blind trial, including an extended series of neuropsychological tests and sham treatments in a multiplace hyperbaric chamber for patients treated with NBO.
                The multiplace hyperbaric chamber at the Alfred Hospital, a university-attached quarternary referral centre in Melbourne providing the only hyperbaric service in the State of Victoria.
                All patients referred with CO poisoning between 1 September 1993 and 30 December 1995, irrespective of severity of poisoning. Pregnant women, children, burns victims and those refusing consent were excluded.
                Daily 100-minute treatments with 100% oxygen in a hyperbaric chamber--60 minutes at 2.8 atmospheres absolute for the HBO group and at 1.0 atmosphere absolute for the NBO group--for three days (or for six days for patients who were clinically abnormal or had poor neuropsychological outcome after three treatments). Both groups received continuous high flow oxygen between treatments.
                Neuropsychological performance at completion of treatment, and at one month where possible.
                More patients in the HBO group required additional treatments (28% v. 15%, P = 0.01 for all patients; 35% v. 13%, P = 0.001 for severely poisoned patients). HBO patients had a worse outcome in the learning test at completion of treatment (P = 0.01 for all patients; P = 0.005 for severely poisoned patients) and a greater number of abnormal test results at completion of treatment (P = 0.02 for all patients; P = 0.008 for severely poisoned patients). A greater percentage of severely poisoned patients in the HBO group had a poor outcome at completion of treatment (P = 0.03). Delayed neurological sequelae were restricted to HBO patients (P = 0.03). No outcome measure was worse in the NBO group.
                In this trial, in which both groups received high doses of oxygen, HBO therapy did not benefit, and may have worsened, the outcome. We cannot recommend its use in CO poisoning. Sixty consecutive patients undergoing elective open-heart surgery were prospectively enrolled in a study to compare the efficacy of 3 different antifibrinolytic drugs to reduce postoperative bleeding and to reduce homologous blood requirements in combination with blood-saving techniques and restrictive indications for blood transfusion. The patients were randomized to 1 of 4 intraoperative treatment regimens: 1) control (no antifibrinolytic therapy); 2) epsilon-aminocaproic acid (10 g IV at induction of anesthesia, followed by infusion of 2 g/h for 5 hours); 3) tranexamic acid (10 mg/kg IV within 30 minutes after induction of anesthesia, followed by infusion of 1 mg/kg per hour for 10 hours); or 4) high-dose aprotinin (2 million KIU IV at induction of anesthesia and 2 million KIU added to the extracorporeal circuit, followed by infusion of 500 thousand KIU/h during surgery). Hemoconcentration and reinfusion of blood drained from the operative field and the extracorporeal circuit after operation were used in all patients. Indications for blood transfusion were hypotension, tachycardia, or both, with hemoglobin values < 8.5 g/dL; or severe anemia with hemoglobin values < 7 g/dL. Compared with the blood loss in the control group, patients receiving aprotinin and epsilon-aminocaproic acid showed significantly less postoperative blood loss at 1 hour (control, 128 +/- 94 mL; aprotinin, 54 +/- 47 mL, p = 0.01; and epsilon-aminocaproic acid, 69 +/- 35 mL, p = 0.03); this trend continued at 24 hours after operation (control, 724 +/- 280 mL; aprotinin, 344 +/- 106 mL, p < 0.0001; and epsilon-aminocaproic acid, 509 +/- 148 mL, p = 0.01). Aprotinin was significantly more efficient than epsilon-aminocaproic acid (p=0.002). Tranexamic acid did not have a statistically significant effect on blood loss. Homologous blood requirements were not significantly different among the groups; postoperative hematologic values and coagulation times were also comparable. Despite the efficacy of aprotinin and epsilon-aminocaproic acid shown in the present study, the blood requirements were not significantly different from those that are found when transfusions are restricted, autotransfusions are used, and blood from the operative field and extracorporeal circuit is concentrated and reinfused. Therefore, intraoperative antifibrinolysis may not be indicated in routine cardiac surgery when other blood-saving techniques are adopted. 27 patients on hemodialysis (dialysate aluminium less than 0.7 mumol/l for 2 years, and 2 mumol/l before) whose plasma Ca and PO4 were adequately controlled for already 6 months by high doses of CaCO3 alone (mean +/- SD: 9 +/- 5 g/day), were randomly divided into 2 groups, a control group (c group) which was kept on the same treatment, and a group in which CaCO3 was reduced to 3 g/day but in which plasma Ca was kept normal due to 1 alpha-OH-vitamin D3 administration (1 microgram/day at the beginning, 0.3 microgram/day after 6 months; 1 alpha group) whereas plasma phosphate was kept below 6.0 mg/dl because of Al(OH)3 (2.7-5 g/day). Initially, the 2 groups were comparable as regards the plasma concentrations of total and ionized Ca, phosphate, alkaline phosphatases, medium and C-terminal parathyroid hormone (PTH) and aluminium, but the control group had lower plasma 25-OH-vitamin D (25-OHD.) After 6 months, the same difference in plasma 25-OHD was found with comparable plasma concentrations of total and ionized calcium as well as of medium and C-terminal PTH (beta error 1%). However, plasma concentration of phosphate and the plasma Ca phosphate product, as well as the plasma aluminium were higher in the 1 alpha group whereas their PCO3H- was lower. Although the alkaline phosphatase values were not significantly different between the 2 groups, they increased only in the control group because of 1 patient who developed a vitamin-D-deficient osteomalacia (plasma 25-OHD 3 ng/ml), which was subsequently cured by physiological doses of 25-OHD3. The incidence of transient hypercalcemia (15 vs. 21 episodes) and worsening of soft tissue calcifications (3 in each group) was the same in the 2 groups.
Preliminary studies suggest benefit from blood alkalinisation with NaHCO3 in OP poisoning, but there is insufficient evidence to support its routine clinical use. Further research is required to determine the method of alkalinisation that will optimise outcomes, and the regimen which will produce the target arterial pH of 7.50 (range 7.45 to 7.55). This should be followed by a well-designed randomised controlled trial to determine efficacy.