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Biomedical subjects

D Safran

Publications and source records attributed to D Safran.

At least 37 records · Page 2Linked to original sources
PubMed1994

Assessment of coagulation factor activation during cardiopulmonary bypass with a new monoclonal antibody.

Antithrombin-III (AT) is a key inhibitor of blood coagulation that neutralizes activated serine esterases by forming covalent modified complexes (ATm). A new monoclonal antibody directed against short-lived AT-activated serine protease complexes provides a means of measuring subclinical coagulation activity during cardiopulmonary bypass (CPB). Twelve patients undergoing CPB for coronary artery bypass grafting were studied and AT, ATm, D-dimers (DD), and several other coagulation and fibrinolytic markers were measured during the surgical procedure. There were decreases in AT, factors V, II, X, IX, protein S (total and free), C4b-binding protein, thrombomodulin, and platelets counts, whereas heparin, ACT, thrombospondin, plasminogen activator inhibitor (PAI-1), and tissue plasminogen activator (tPA) increased. ATm and the percentage of ATm available (ATm/AT) showed a peak during CPB. These results demonstrate that during CPB, the use of heparin produces an equilibrium involving increased coagulation activation and consumption in association with increased fibrinolysis. The equilibrated consumption of both coagulation and fibrinolytic factors leads to low levels of all factors after cardiac surgery. The ATm assay allows assessment of the differential effects of CPB and surgical trauma on coagulation activation. It is speculated that ATm levels may be useful in monitoring the consumption of coagulation factors.

Adult↗
PubMed1994

Hemofiltration during cardiopulmonary bypass in pediatric cardiac surgery. Effects on hemostasis, cytokines, and complement components.

BACKGROUND: This prospective study was intended to determine in a homogeneous population of children whether hemofiltration, performed during cardiopulmonary bypass rewarming, is able to improve hemodynamics and biologic hemostasis variables, to reduce postoperative blood loss, time to extubation, and plasma cytokines, and complement fragments. METHODS: Thirty-two children undergoing surgical correction of tetralogy of Fallot were randomly assigned to a hemofiltration or control group. Hemofiltration was performed with a polysulphone hemofilter during rewarming of cardiopulmonary bypass. Plasma clotting factors, D-dimers, antithrombin-III, complement fragments C3a and C5a, interleukin-1 beta, interleukin-6, interleukin-8, and tumor necrosis factor-alpha were measured before and after hemofiltration. Systemic mean arterial pressure, left atrial pressure, time to extubation, and postoperative blood loss were monitored. RESULTS: In the hemofiltration group, significant reductions in 24-h blood loss (250 (176-356) vs. 319 (182-500) ml/m2, median (minimum-maximum), time to extubation (15 (9-22) vs. 19 (11-24) h), plasma concentrations of C3a, C5a, interleukin-6, and tumor necrosis factor-alpha were observed compared to control. Arterial oxygen tension on admission to the intensive care unit was significantly greater in the hemofiltration group (136 +/- 20 vs. 103 +/- 25 mmHg, mean +/- SD). Significant increases in mean arterial pressure, clotting factors, and antithrombin-III were noted for the hemofiltration group. No intergroup difference was observed in left atrial pressure, platelets count, D-dimers, interleukin-8, and duration of stay in the intensive care unit. CONCLUSIONS: Hemofiltration during cardiopulmonary bypass in children improves hemodynamics and early postoperative oxygenation and reduces postoperative blood loss and duration of mechanical ventilation. Hemofiltration is able to remove some major mediators of the inflammatory response.

Cardiopulmonary Bypass↗
PubMed1994

Inhaled nitric oxide as a therapy for pulmonary hypertension after operations for congenital heart defects.

Seventeen infants were treated with inhaled nitric oxide for critical pulmonary artery hypertension after operations for congenital heart defects. In all 17 patients conventional medical therapy consisting of hyperventilation, deep sedation/analgesia, and correction of metabolic acidosis had failed. All children were monitored with a transthoracic pulmonary artery catheter inserted at operation. Pulmonary artery hypertension was defined as an acute rise in pulmonary pressure associated with a decrease in oxygen arterial or venous saturation. After failure of conventional medical therapy, 20 ppm of inhaled nitric oxide was administered to the patient. In all patients the pulmonary pressures decreased (mean pulmonary arterial pressure decreased by -34% +/- 21%) without significant change in systemic arterial pressure, whereas the oxygen arterial saturation and oxygen venous saturation increased by 9.7% +/- 12% and 37% +/- 28%, respectively. Fifteen children were discharged from the intensive care unit at 10 +/- 6 days (range 3 to 26 days) and two died. This study demonstrates that inhaled nitric oxide exerts a selective pulmonary vasodilation without decreasing systemic arterial pressure in children with congenital heart disease. The increased values of mixed venous oxygen saturation and urinary output suggest that this selective lowering of pulmonary vascular resistance improved the overall hemodynamics. The potential toxic effects of nitric oxide and nitrogen dioxide necessitate careful consideration of the risks and benefits of inhaled nitric oxide therapy.

Acute Disease↗
PubMed1993

[Continuous monitoring of mixed venous blood oxygen saturation].

Mixed venous oxygen saturation (SvO2), measured on pulmonary artery blood, is a convenient indicator of matching between O2 transport (TaO2) and O2 body consumption (VO2). The measurement technique is based on the haemoglobin reflection spectrophotometry principle using two or three wave lengths. The Fick principle points out that SvO2 depends on five parameters: SvO2 = SaO2 - (VO2/CI x Hb x PO) where SaO2, CI and PO respectively represent arterial O2 saturation, cardiac index and O2 affinity. SvO2 does not always reflect tissue O2 tension: when considering a given value of SvO2, PvO2 will depend upon the position of the oxyhaemoglobin dissociation curve. It is impossible to establish in the absolute a "normal" value of SvO2. However, in most clinical circumstances, an SvO2 ranging from 60 to 80% attests that O2 tissue delivery is appropriate. Under certain conditions a continuous monitoring of SvO2 allows to assess another index such as ventilation-perfusion index or the O2 tissue extraction index. Usually SvO2 variations are more informative than the absolute SvO2 value. However, their interpretation should be cautious. First and foremost, the ability of each of the four main SvO2 determinants to influence the SvO2 is unequal as the numerical ranges of variation of these determinants are very different. Moreover, the attribution of a variation of SvO2 to one of its determinants implies that each of them is independent from the others, a feature which is very rarely seen in clinical practice. Finally as the mathematical relationship between SvO2 and its determinants is linear (SaO2 and VO2), or hyperbolic (CI and Hb), the weight of SaO2 or VO2 is independent of their absolute value, whereas CI or Hb weights will depend on their value. The limits of SvO2 monitoring are linked first to the occurrence of an anaerobic metabolism state when TaO2 becomes too low; SvO2 then just provides informations on the aerobic part of the metabolism. Moreover, SvO2 is just a global indicator for tissue O2 oxygenation status which does not give any indication about regional flow distribution. Therefore, SvO2 enables systemic imbalance supervision only. Finally, the existence of a right-to-left shunt will modify the SvO2 values through various mechanisms. However the SvO2 measured, in the pulmonary artery, remains reliable, whereas the presence of a left-to-right shunt will highly alter SvO2 basal value, only its time course remaining significant. SvO2 monitoring, element of diagnosis and monitoring, as well as a warning signal, has a priori specific indications poorly assessed, so far. (ABSTRACT TRUNCATED AT 400 WORDS)

Cardiac Surgical Procedures↗
PubMed1993

[Control of the ratio of the flow rate of the substitution fluid to the blood removal rate during preoperative normovolemic hemodilution].

Twenty-one patients (mean age 46 +/- 13 years) due to undergo abdominal or ENT surgery, presumed to give rise to an important blood loss were included in this study. None had any contra-indication to the use of normovolaemic haemodilution (NH). Mean initial haematocrit was 40.3 +/- 1.8%. Their estimated total blood volume was 4,867 +/- 857 ml. The patients were anaesthetized with thiopentone, fentanyl, vecuronium or atracurium. Maintenance was carried out with isoflurane (0.5% during NH). Usual haemodynamic monitoring was used throughout. The required haematocrit was decided on before starting NH. The amount of blood to be removed was calculated with usual mathematical formulae. A radial artery cannula (n = 7), or a subclavian or femoral venous cannula (n = 14) was used to remove blood, which was collected within a bag containing CPC-adenine. Six % hydroxyethyl starch (Elohes) was given through a short venous cannula some distance from the first one. An antiparallel double line set in a roller pump was used to carry out the NH. A mean 1,341 +/- 405 ml of blood were withdrawn so as to reach a mean haematocrit of 30.6 +/- 2.4%. NH was completed within 17 +/- 6 min. No major haemodynamic changes occurred during the procedure. No significant differences were observed between expected and observed final haematocrits. There was no effect of the volume of blood withdrawn on the error of haematocrit prediction (0.5 +/- 0.3%). However, a higher rate of blood removal could increase this error. This easy-to-use device seems to provide fast and identical rates of blood removal and replacement. The expected haematocrit may thus be reached reliably, even if this must be checked for the sake of safety.

Adult↗
PubMed1993

Laparoscopy in high-risk cardiac patients.

Fifteen patients with severe cardiac disease (American Society of Anesthesiologists III or IV) underwent laparoscopy using radial artery and pulmonary artery catheters to determine intraoperative hemodynamic changes. Cardiac output (CO), mean arterial blood pressure (MAP), central venous pressure, heart rate, systemic vascular resistance (SVR) and mixed venous oxygen saturation (SVO2) were recorded before anesthetic induction, after induction, but before peritoneal insufflation, after insufflation and after release of pneumoperitoneum. Peritoneal insufflation led to significant elevations in MAP and SVR and reduction in CO. For seven patients, a decrease in SVO2 after peritoneal insufflation was predictive of significant worsening of hemodynamic parameters, suggesting inadequate cardiac reserve. In all patients, hemodynamic parameters returned toward baseline once pneumoperitoneum was released. There were no perioperative cardiac complications. While it is evident that laparoscopy presents serious hemodynamic stress, it can be performed safely in high-risk patients, using aggressive intraoperative monitoring.

Adult↗
PubMed1991

Inflammatory pseudotumors of the spleen.

Inflammatory pseudotumors are uncommon benign lesions that have been found in numerous organ systems. However, their appearance within the spleen is decidedly rare. Grossly, pseudotumors appear as well-circumscribed, encapsulated masses, while microscopic examination reveals a polymorphous inflammatory cell infiltrate occurring variably with granulomatous reaction, fibrosis, and cell necrosis. Because they often present either as unexplained, asymptomatic masses or with vague constitutional symptoms, splenic inflammatory pseudotumors can raise suspicion for a primary splenic neoplasm, such as lymphoma. Splenectomy is the treatment of choice.

Female↗
PubMed1991

[Continuous hemofiltration: an extrarenal filtration method used in intensive care].

Continuous haemofiltration (CHF) mimics physiological glomerular filtration. Blood flows through a haemofilter, which is permeable to water and to all those substances not bound to plasma proteins, of up to about 6,000 d molecular weight. Ten to twenty liters of ultrafiltrate (UF) can be filtered daily. Solute concentration in this UF is very similar to that in plasma water. Because of the large volumes involved, the UF must be replaced continuously with an electrolyte solution. Electrolyte and acid-base disturbances can thus be easily and rapidly corrected. There are different techniques of CHF. Continuous arteriovenous haemofiltration (CAVH) avoids the use of an external blood pump, as the patient's own arterial pressure is used to drive the blood through the filter via a large-bore arterial catheter. On the other hand, continuous venovenous haemofiltration (CVVH) requires the use of a blood pump with a pressure alarm and an air bubble detector. Supplementary diffusive transport [CAVH(D),CVVH(D)] can improve the clearance of low molecular weight toxins, such as urea. In these techniques, there is a continuous flow of dialysate in the UF compartment of the haemofilter. One of the major problems with CHF is the anticoagulation of patients who are at risk of developing haemorrhagic complications. Unfractionated heparin is used most often, but other drugs have been used: low molecular weight heparin, prostacyclin, nafamostat, or sodium citrate. The neutralization of heparin has also been suggested. Because the fluid balance can be easily managed by CHF, patients in acute renal failure can be given standard intravenous feeding. Many small endogenous molecules, such as gastrin, are probably removed by CHF. However, most drugs have a molecular weight less than 6,000 d, and are not totally protein-bound. They are therefore likely to be ultrafiltered, and so, become inefficient. As a result, the drugs used should be adapted to the haemofilter, and vice versa. More than any extracorporeal circulation, CHF increases the incidence of bacterial blood contamination, because of its continuous use. Routine blood cultures should be carried out. Moreover, blood is cooled during its passage in the extracorporeal circuit, leading to hypothermia. There are some devices which prevent this. Renal function can be completely replaced with the production of 12 to 15 l UF a day. CHF must be started early on in the course of the renal failure. When the concentration of blood urea is greater than 40 mmol.l-1 diffuse transport must also be used.(ABSTRACT TRUNCATED AT 400 WORDS)

Acid-Base Equilibrium↗
PubMed1991

[Determination of elimination of pefloxacin and of its derivatives in continuous hemodiafiltration].

Continuous venovenous hemofiltration with dialysis (CVVHD) is being increasingly used to treat acute renal failure. However, because of the-lack of data on the clearance of therapeutic agents during this treatment, there is a risk of using inappropriate dosages. This in vitro study was undertaken to determine the clearance of pefloxacin (P) and its two main metabolites (active N-desmethyl P and inactive N-oxide P) during CVVHD. Acitrate-dextrose (ACD) anticoagulated fresh human blood containing P and its two metabolites in the usual therapeutic levels was circulated at a rate of 100 ml min.-1 through a closed-circuit continuous venovenous hemofiltration with dialysis unit (BSM 22-Hospal hemofilter). Temperature and ionic composition of the blood were controlled. Dialysate (L2D, Hospal) was circulated on the other side of the continuous venovenous hemofiltration with dialysis membrane at three different flow rates (Qdi) (0, 500 and 1,000 ml.h-1. The dialysate/ultrafiltrate outflow was adjusted using a withdrawal pump to obtain nul ultrafiltration. Arterial blood, venous blood and ultrafiltrate were sampled simultaneously at different time points for High Performance Liquid Chromatography (HPLC) assays and determination of the clearances (Cl) and sieving coefficients (s) of each compound. Pefloxacin had a sieving coefficient of 0.42 and a clearance of 6.8 ml min-1 when Qdi was nul. With the blood flow used, clearances were found to be correlated with the dialysate flow rate; when this rate was 500 ml h-1, a pefloxacin clearance similar to that seen in healthy subjects was obtained (15.2 ml min-1). The two bacteriologically active forms of the drug (pefloxacin and N-desmethyl P) had similar elimination parameters.(ABSTRACT TRUNCATED AT 250 WORDS)

Dialysis↗
PubMed1990

[Comparison of the antithrombotic effects of heparin, enoxaparin and prostacycline in continuous hemofiltration].

Continuous anticoagulation is required during haemofiltration to prevent the deposition of fibrin and the formation of thrombus which would lead to early clotting of the haemofilter. This study aimed to compare the efficiencies of 3 different anticoagulation protocol: 150 IU.kg-1.day-1 heparin (group HEP), 1.2 mg.kg-1.day-1 enoxaparin (group ENX), and a combination of 0.8 mg.kg-1.day-1 enoxaparin with 5 ng.kg-1.min-1 prostaglandin I2 (group ENX and PGI2). A flat ANS69S (Hospal) haemofilter was used for continuous venovenous haemofiltration. Antithrombotic efficiency was assessed with a haemofilter permeability index (HPI) including the transmembraneous pressure gradient and the rate of production of ultrafiltrate. The time required for HPI to decrease to 1/3 of its initial value (HPI1/3) was used to compare the 3 protocols. Treatment tolerance was judged by monitoring the usual haemodynamic and haemostatic parameters. No adverse effects (bleeding, thrombosis, hypotension) were observed. HPI1/3 was 15.1 +/- 2.4 h, 18.3 +/- 3.1 h and 28.2 +/- 4.2 h in groups HEP, ENX and ENX and PGI2 respectively. High dose enoxaparin reached antithrombotic efficiency without increasing the risk of haemorrhage. The use of low doses of prostaglandin I2 greatly increased HPI1/3, without any deleterious haemodynamic effects. However, the high cost of prostaglandin I2 needs to be put in the balance with the increase in duration of haemofilter life. Therefore, further investigations are required to evaluate the possible synergy between heparin and prostaglandin I2, as well as the biological parameters which need to be monitored.

Acute Kidney Injury↗
PubMed1990

Continuous intercostal blockade with lidocaine after thoracic surgery. Clinical and pharmacokinetic study.

The efficacy and the side effects of a continuous infusion of lidocaine in the fifth intercostal space for the management of postoperative pain after lateral thoracotomy were evaluated in 20 adults. An indwelling catheter was inserted in the appropriate intercostal space before thoracotomy closure. After recovery from general anesthesia, a loading dose of 3 mg/kg of 1.5% lidocaine with epinephrine 1:160,000 was injected through the catheter, followed by a continuous infusion of 1% lidocaine without epinephrine at a rate of 1 mg.kg-1.h-1 for 54 h. In seven patients pharmacokinetic data were obtained. Pain, assessed by visual continuous analog scale, decreased from a median score of 8 (range, 7-10) to a score of 5 (range, 2-7) 20 min after the loading dose of lidocaine and continued to decrease until the end of the study (P = 0.0001). Complete cutaneous analgesia, assessed by pinprick test, was seen in a median of three thoracic spinal segments (range, 0-6) with partial cutaneous analgesia in seven segments (range, 6-9) 40 min after the loading dose, and levels that remained unchanged for 54 h (P = 0.0001). Peak lidocaine serum concentrations, 1.9 +/- 0.7 micrograms/mL, were present 9 +/- 3 min after injection of the loading dose. Serum concentrations of lidocaine under steady state conditions averaged 4.8 +/- 0.9 micrograms/mL (range, 3.5-5.8 micrograms/mL). This level under steady state conditions, though below the toxic level, suggests that additional bolus injection of lidocaine during the course of infusion might result in potentially toxic serum levels of lidocaine.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1990

Spontaneous splenic rupture following infectious mononucleosis.

Four cases of spontaneous splenic rupture after infectious mononucleosis (IM) have been treated at this institution since 1978. The condition is rare, occurring in 0.1-0.5 per cent of patients with proven infectious mononucleosis. Splenectomy is considered the treatment of choice for these patients. However, because recent trends in the management of traumatic splenic rupture are moving towards nonoperative treatment with selected patients, a similar approach has been considered for the patient with spontaneous splenic rupture following IM. The major reason for avoiding splenectomy is the increased incidence of sepsis in splenectomized patients. Yet, splenic rupture is accompanied by hemorrhage and the risks associated with blood transfusion for ongoing hemorrhage are of similar magnitude as those of sepsis following splenectomy. In addition, the grossly abnormal spleens seen at operation tend to include large, contained hematomas that may also be prone to rupture. Therefore, operative management still appears to be the preferred treatment for spontaneous splenic rupture following IM. Splenectomy is curative, safe, and obviates the need for transfusion, extended hospitalization, and activity restriction.

Adult↗
PubMed1989

[Continuous monitoring of mixed venous oxygen saturation in anesthesia in pulmonary surgery].

The multiplicity of potential causes of variations in mixed venous oxygen saturation (SvO2) during one lung ventilation (OLV), including a constant ventilation/perfusion mismatch, explains that it has been suggested as a routine monitoring procedure. To assess its usefulness, 12 adults undergoing OLV were monitored during surgery with an Oximetrix pulmonary catheter, placed on the side opposite to the surgical field under fluoroscopic control. Seventy two complete sets of haemodynamic measurements were obtained at 6 different times during surgery. We studied the ability of changes in SvO2 to predict changes in arterial oxygen saturation (SaO2), cardiac output (CO), and venous admixture (VA) by calculating sensitivities (Se), specificities (Sp) and predictive values with regard to these variables. There were no complications due to the protocol. However left-sided catheter placement failed in four cases. Correlation between optical and measured SvO2 was very strong (r = 0.94; p less than 0.001). SvO2, oxygen consumption (VO2) and the rate of oxygen extraction remained constant throughout the procedure, even when CO, mean arterial pressure, VA, SaO2 and PaO2 varied. Clamping the pulmonary artery returned VA, SaO2 and PaO2 values to those found before OLV, but produced a significant decrease in CO. SvO2 had low Se and Sp for changes in other variables (CO: 76 +/- 7, 48 +/- 9; PaO2: 79 +/- 6, 59 +/- 9; VA: 54 +/- 7, 48 +/- 7 respectively). In this type of surgery, alterations in variables related to oxygen are probably balanced by haemodynamic changes. In fact, according to Fick's formula, SvO2 is almost completely determined by SaO2 and CO, when VO2 and haemoglobin remain stable.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗