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L R Sehgal

Publications and source records attributed to L R Sehgal.

At least 19 recordsLinked to original sources
PubMed2002

The use of low molecular weight heparins for the prevention of postoperative venous thromboembolism in general surgery. A survey of practice in the United States.

BACKGROUND: Even though low molecular weight heparins (LMWHs) have become the standard for venous thromboembolism (VTE) prophylaxis in most European countries and Canada, it was not until recently that LMWHs were approved for use in the United States. The main objective of this study was to assess the current preferences and attitudes of United States surgeons toward the prevention of VTE with particular reference to LMWH. METHODS: A survey with questions relative to VTE awareness, risk factors, and prevention practices was mailed to 10,000 Fellows of the American College of Surgeons. RESULTS: A total of 1,145 (11.45%) usable questionnaires were returned. The vast majority (96%) of respondents use prophylaxis against VTE. Although LMWHs were rated first regarding efficacy and second regarding simplicity of use, conventional unfractionated heparin at fixed doses remains the preferred pharmacological agent for VTE prevention (74%), followed by 2 LMWHs: enoxaparin (34%) and dalteparin (16%). Overall, 52% of surgeons preferred physical methods over pharmacological methods when used separately and 26% of surgeons utilize combined physical-pharmacological modalities. CONCLUSIONS: North American general surgeons have substantially modified their approach to VTE prevention in the last 4 years. Physical methods and unfractionated heparin remain the preferred prophylactic modalities, but LMWHs have gained rapid acceptance since their approval for use for VTE prevention in North America. Even though the results of this survey must be interpreted with caution because of the limited response rate and possible sampling bias, they still reflect the current preferences and attitudes of North American surgeons toward prophylaxis.

Anticoagulants↗
PubMed2001

Evaluation of oxygen extraction ratio as a physiologic transfusion trigger in coronary artery bypass graft surgery patients.

BACKGROUND: Approximately 20 percent of all allogeneic blood transfusions are administered in connection with coronary artery bypass graft (CABG) operations. Transfusion practices vary across the country. The whole-body oxygen extraction ratio (O2 ER) reflects the adequacy of the patient's response to acute normovolemic anemia with an O2 ER of approximately 50 percent being shown to be an appropriate transfusion trigger. The present study monitored the O2 ER in patients undergoing CABG and determined if transfusion practices would have been different if an O2 ER > or = 45 percent were used as a transfusion trigger. STUDY DESIGN AND METHODS: Seventy patients with a postoperative Hct < = 25 percent were the test subjects. Arterial and mixed venous contents were determined before the operation, in the intensive care unit after the operation, and 12 hours after the operation. RESULTS: There were no deaths. Forty-one patients received allogeneic transfusion. These patients were older, weighed less, and had a preoperative Hct lower than the nontransfused patients. There were no significant differences between transfused and nontransfused patients with respect to postoperative Hct (21.0 +/- 0.4 vs. 22.2 +/- 0.4), cardiac index (2.5 +/- 0.1 vs. 2.7 +/- 0.1), O2 delivery (6.4 +/- 0.3 vs. 6.7 +/- 0.3), O2 consumption (2.5 +/- 0.1 vs. 2.5 +/- 0.1), and O2 ER (38.3 +/- 1.7 vs. 37.5 +/- 1.5). In the transfusion group, 7 of 21 patients had a postoperative O2 ER > or = 45 percent, while 3 of 35 in the nontransfused group had that result. CONCLUSION: The use of O2 ER as a transfusion trigger as part of a transfusion algorithm could lead to a reduction in allogeneic blood transfusion.

Aged↗
PubMed2001

Home use of impulse compression of the foot and compression stockings in the treatment of chronic venous insufficiency.

PURPOSE: The use of intermittent pneumatic compression, in addition to elastic bandages or stockings, accelerates the healing of leg ulcers in patients with severe chronic venous insufficiency (CVI). There is recent evidence that impulse compression of the plantar venous plexus reduces post-traumatic ankle swelling and prevents postoperative venous thromboembolism. The purpose of this study was to evaluate the clinical and hemodynamic responses after home use of impulse foot compression for 3 months in patients already using therapeutic compression stockings for the management of CVI. METHODS: Twelve extremities from 9 patients with documented CVI, class 4 to 5 according to the Clinical, Etiology, Anatomy, Pathophysiology classification system, were included in this prospective cohort study. All patients were instructed to use a foot pump device at home for 2 hours a day for 3 months in addition to therapeutic compression stockings (30-40 mm Hg) worn during the day. The device was set to three cycles (3 seconds) of compression (120 mm Hg) per minute. A clinical scoring system was completed before foot compression and 1, 2, and 3 months thereafter. In addition, all patients underwent air plethysmography studies at the same time intervals, including venous volume, venous filling index, ejection fraction, and residual volume fraction. RESULTS: Patients reported significant improvement in their scores for swelling (P <.05) and pain (P <.04). Air plethysmography showed a reduction in venous volume and venous filling index, although these differences were not significant. Ejection fraction remained unchanged and residual volume fraction was significantly reduced (P <.05) compared with baseline. The foot compression devices were well tolerated by all the patients in the study. CONCLUSIONS: The use of home foot impulse compression plus elastic stockings significantly reduced the residual volume fraction as measured by air-plethysmography in a group of patients with severe CVI. This favorable hemodynamic response could, in part, explain the clinical improvement achieved by this combined treatment. However, this represents a preliminary pilot study that needs to be confirmed in future randomized controlled studies with more patients included.

Bandages↗
PubMed1995

The development of hemoglobin solutions as red cell substitutes: hemoglobin solutions.

Although the efficacy of hemoglobin-based oxygen carriers was established more than 60 years ago, all prior clinical trials have demonstrated significant toxicity characterized by renal dysfunction, gastrointestinal distress, and systemic vasoconstriction. The mechanisms of these toxicities now appear to be understood. Tetrameric forms of the hemoglobin molecule extravasate from the circulation and interact with endothelial derived relaxing factor, leading to unopposed vasoconstriction. Although numerous efforts are underway to chemically modify the native tetramer, it is likely that all tetrameric forms of the hemoglobin molecule will continue to extravasate. We have focused on developing a polymerized form of hemoglobin that is virtually free of unreacted tetramer. The development and characterization of this polymerized pyridoxylated hemoglobin solution (Poly SFH-P) is described. Clinical trials have been completed successfully in volunteers, and are now underway to assess the safety and efficacy of Poly SFH-P as a clinically useful red cell substitute in the treatment of acute blood loss in the setting of trauma and surgery.

Animals↗
PubMed1993

Effects of recombinant human erythropoietin and interleukin-3 on erythropoietic recovery from acute anemia.

The risks inherent in the use of homologous blood products have increased efforts toward identifying alternatives to transfusion. We have previously shown that the administration of recombinant human erythropoietin (rhEpo) enhances the erythropoietic response to acute blood loss. Recombinant human interleukin-3 (rh-IL-3) is a hematopoietic growth factor that has been shown to act synergistically with rhEpo in accelerating erythropoiesis in vitro. The purpose of this study in a primate model was to determine if the administration of rhIL-3 in combination with rhEpo could augment the erythropoietic response to acute blood loss more than rhEpo therapy alone. Twenty-four adult male baboons were randomized into four groups. The induction of acute normovolemic anemia to a hematocrit of 20% was accomplished via exchange-transfusion with 6% hetastarch. The groups were then treated for 7 consecutive days with the following growth factors: group I (n = 7), no growth factors; group II (n = 5), rhIL-3 alone (100 micrograms/kg/d); group III (n = 6), rhEpo alone (1000 U/kg/d); group IV (n = 6), rhEpo (1000 U/kg/d) plus rhIL-3 (100 micrograms/kg/d). All animals received folate, vitamin B12, and intravenous iron-dextran immediately following the exchange-transfusion. Response to therapy was monitored for 35 days. There were no adverse reactions following growth factor administration. The analysis of erythropoietic rates between study days 1 through 11, as determined via linear regression analysis, revealed that hematocrits increased significantly faster in the groups receiving rhEpo compared to controls. The administration of rhIL-3, however, did not increase the rate of erythropoiesis when compared to controls, nor did it augment response when added to the rhEpo regimen. The results of this study demonstrate that the administration of rhIL-3 alone had no significant effect on erythropoiesis in this setting of acute blood loss. Further, despite promising in vitro data, rhIL-3 provided no additional stimulation of erythropoiesis in animals receiving rhEpo. Nevertheless, the study confirms that the pharmacologic acceleration of erythropoiesis by rhEpo alone remains an attractive alternative to homologous transfusion.

Acute Disease↗
PubMed1993

Hypovolemic shock.

This article defines a rational approach to the treatment of hemorrhagic shock. All patients that are hypovolemic following hemorrhage require fluid resuscitation. Some patients require red cell restoration and very few require correction of any clotting deficiencies. A physiologic approach to these problems will lead to optimal patient care in these circumstances.

Blood Transfusion↗
PubMed1992

Oxygen extraction ratio: a valid indicator of transfusion need in limited coronary vascular reserve?

We have described whole body oxygen (O2) extraction ratio (ER) as a reliable indicator of transfusion need in acute normovolemic anemia. In normal hearts, myocardial lactate production (-LACT), indicating anaerobic metabolism, does not occur until the ER greater than 50% and Hct less than 10%. It is not known if the ER is valid in the setting of limited coronary vascular reserve. This study assesses the effect of a critical left anterior descending (LAD) coronary stenosis on the compensation to acute blood loss anemia. Adult dogs were anesthetized, paralyzed, and mechanically ventilated. A critical LAD stenosis was created in seven animals (STEN). There were seven controls (CON). Animals underwent isovolemic exchange transfusion with 6% HES until cardiac failure (CF). Catheters were placed in the aorta, pulmonary artery, and anterior interventricular coronary vein. Cardiac failure occurred at Hct = 8.6% +/- 0.4% in the CON and 17.0% +/- 0.5% in the STEN animals. Cardiac output increased in the CON, but not in the STEN animals. Blood flow in the LAD increased in the CON but not the STEN animals. -LACT began in the CON and STEN animals at Hct less than 20% and coincided with an ER greater than 50% in both groups. We conclude that CF occurs at a higher hematocrit with a critical LAD stenosis. The whole body ER greater than 50% remains a valid indicator of myocardial metabolism in anemia in the presence of limited coronary vascular reserve. The ER may be a useful guide to transfusion therapy.

Anemia↗
PubMed1992

Artificial blood: current status of hemoglobin solutions.

Attempts to develop a hemoglobin-based red cell substitute have spanned many decades, but no clinically useful product has been produced to date. The issues preventing clinical application primarily are ones of safety--not efficacy. Numerous animal studies have documented the efficacy of SFH. Although effective, the solution has limitations that have caused concern. Oncotic considerations limit the concentration of the infusate SFH to 6 to 8 g/dL, or half-normal. Owing to the loss of organic phosphate modulators of P50, such as 2,3-DPG, the P50 of SFH is typically between 12 and 14 mm Hg, which is also half the normal value. And finally, the intravascular half-life of SFH is too short, ranging only from 2 to 6 hr. Polymerization provides a means of correcting these limitations. The high oxygen affinity can be greatly diminished by covalent binding of pyridoxal-5'-phosphate to the N-terminal of the chains. Colloid osmotic pressure exerted by a protein solution is proportional to the number of discrete colloid particles. Through polymerization, the number of colloid particles is reduced, leading to a decrease in COP. Data show that this can be achieved in a reproducible fashion. The rate at which COP diminishes determines the yield of polymeric species, as well as their molecular weight distribution. Polymerization can be controlled to result in a yield of 75% to 85% polymers with a molecular weight distribution of 128 to 400 kd. The number average and the weight average molecular weights indicate that the large proportion of polymers represent the cross linking of two tetramers. The data that reflect the interaction of oxygen with poly-SFH-P indicate that the oxygen carrying function of hemoglobin has not been significantly altered by the chemical modifications. The binding coefficient of oxygen is unchanged. As anticipated, there is a loss of cooperativity (diminished Hill coefficient) between the hemoglobin chains, suggesting structural restrictions in the polymeric species because of cross linking. A reduced alkaline Bohr effect is the expected result, and data confirm this. Finally, some increase in oxygen affinity is to be expected with polymerization. This is indeed the case, although the P50 of poly-SFH-P is comparable to banked blood (18 to 22 mm Hg). To be clinically useful, a modified hemoglobin solution requires a reasonable shelf-life.(ABSTRACT TRUNCATED AT 400 WORDS)

Blood Gas Analysis↗
PubMed1991

Erythropoietin deficiency after coronary artery bypass procedures.

Erythropoietin is the primary regulator of erythropoiesis. Erythropoietin has been shown to increase exponentially in response to linear decreases in hematocrit in normal, unstressed animals. However, the effect of operation, with its attendant stress, on erythropoietin levels is unknown. The purpose of this study is to evaluate the effect of surgical stress on erythropoietin. Twenty otherwise healthy patients scheduled for elective surgical procedures were studied. The cholecystectomy group included 10 patients who underwent cholecystectomy for documented stone disease. Ten patients who underwent coronary artery bypass procedures constituted the coronary artery bypass grafting group. Patients were studied preoperatively as well as on the first and second postoperative days. The hematocrit and erythropoietin levels were similar in both groups preoperatively. The hematocrit in the coronary artery bypass grafting group was lower than that of the cholecystectomy group on postoperative day 1 (0.31 versus 0.36; p less than 0.003) and postoperative day 2 (0.30 versus 0.36; p less than 0.001). During the first two postoperative days the erythropoietin levels were similar between groups. The data show that postoperative erythropoietin levels are similar after coronary artery bypass grafting, despite more severe anemia, when compared with cholecystectomy. This suggests that after coronary artery bypass grafting there is a relative deficiency of erythropoietin. Administration of recombinant human erythropoietin to patients undergoing surgical procedures could correct the erythropoietin deficiency and accelerate postoperative erythropoiesis.

Adult↗
PubMed1990

The efficacy of polymerized pyridoxylated hemoglobin solution as an O2 carrier.

A polymerized pyridoxylated hemoglobin solution (Poly SFH-P) has been prepared with a normal [Hb] of 14 g/dL, a normal COP of 20 to 25 torr, a P50 of 16 to 20 torr, and a plasma T1/2 of 40 to 46 hours. Animals underwent a total exchange transfusion with Poly SFH-P to assess its ability to support hemodynamics and oxygen transport in the absence of red cells. All animals survived the exchange transfusion. Mean arterial pressure (MAP), heart rate (HR), cardiac output (CO), and oxygen consumption (VO2) remained at baseline values at zero hematocrit after the exchange. The final plasma [Hb] at Hct less than 1% was 9.7 +/- 0.4 g/dL. These results are significantly better than previous data with unmodified tetrameric hemoglobin solution (SFH). Poly SFH-P supports life in the absence of red cells. In contrast to SFH, Poly SFH-P achieves a nearly normal [Hb], a longer T1/2, and maintains baseline hemodynamics and oxygen consumption at zero hematocrit. These results document that Poly SFH-P is an effective oxygen carrier that offers greater potential than previous products as a clinically useful red cell substitute.

Animals↗
PubMed1990

Erythropoietic response to acute anemia.

Reliance on a brisk erythropoietic response to untreated blood loss is an alternative to transfusion of homologous blood. Slow erythropoiesis has been observed in ICU patients who refused blood. Many of these patients received supplemental oxygen therapy and Fluosol-DA, a temporary red cell substitute. This study reports the erythropoietic response, in the baboon, to moderate (Hct 20%) and severe (Hct 10%) anemia. In addition, the effect of oxygen therapy (FIO2 0.6 for 1 wk) and fluorocarbon emulsions (Oxypherol) on erythropoiesis was evaluated. Baboons uniformly survived acute normovolemic anemia with Hct 10%. In all cases, the response to anemia was characterized by a lag period (with no change in Hct), and a nonlinear recovery period. A lag period of 3 days was observed in both moderate and severe anemia for baboons breathing room air or FIO2 0.6. The lag period was prolonged to 1 wk in the presence of Oxypherol. The recovery period exhibited a uniform and negative correlation between the rate of Hct change and the Hct, in all cases. The theoretical maximum rate of increase of Hct was 2.6%/day. In untreated blood loss, shortening the lag period and increasing the slope of the recovery period will decrease the length of time that the patient is anemic.

Acute Disease↗
PubMed1990

Effect of hemoglobin solution on compensation to anemia in the erythrocyte-free primate.

Hemoglobin solutions are undergoing clinical trials as erythrocyte substitutes. Some of these solutions have higher O2 affinities compared with normal erythrocyte hemoglobin. Also, they appear to interact with endothelial-derived smooth muscle relaxation. The purpose of this study was to evaluate the nature and limits of compensation to acute normovolemic anemia in the erythrocyte-free primate maintained with a hemoglobin solution. The experimental group consisted of six anesthetized paralyzed adult baboons (Papio anubis) that were exchange transfused (ET) with a pyridoxylated polymerized hemoglobin solution [hemoglobin concentration [( Hb]) = 14 g/dl, O2 half-saturation pressure of hemoglobin (P50) = 19.6 Torr] until a hematocrit less than 1% was achieved. They underwent a second ET with Dextran-70 until [Hb] = 1 g/dl. A control group (n = 6) underwent an ET with Dextran-70 until [Hb] = 1 g/dl. Both groups maintained O2 consumption (VO2) until [Hb] = 3 g/dl. Both groups were stable until [Hb] less than 1 g/dl, and both groups increased their cardiac output. The relation between VO2 and O2 delivery was similar for both groups. In vivo P50 and mixed venous O2 tension were significantly lower in the experimental group. The nature and limits of compensation to diminished O2 delivery due to anemia were similar in the two groups.

Anemia↗
PubMed1989

Treatment of acute postoperative anemia with recombinant human erythropoietin.

Risks inherent in the administration of blood products have increased efforts to avoid homologous transfusion. Although this has increased interest in autologous transfusion and intraoperative salvage, little attention has been focused on efforts to enhance endogenous erythropoiesis as a method of minimizing exposure to homologous blood. Recombinant human erythropoietin (rHuEPO) has been shown to enhance erythropoiesis. The purpose of this study is to evaluate the effect of rHuEPO, administered postoperatively, on a model of acute blood loss. Eleven adult male baboons were randomized into two groups. All animals underwent a laparotomy and an exchange transfusion, with 6% hetastarch, to a final hematocrit of 15%. Group I (N = 6) received 1,000 units/kg of recombinant human erythropoietin daily for the first 14 postoperative days. Group II (N = 5) received an equivalent volume of placebo. All animals were given supplemental vitamin B12, folate and 200% of shed iron, as iron dextran IV, after exchange transfusion. Response was observed for a period of 35 days. All animals survived the protocol. There were no adverse reactions to rHuEPO or surgical complications. The hematocrits were similar between groups at baseline and after exchange transfusion. The maximal rate of erythropoiesis was significantly faster in the rHuEPO group (2.1 vs. 1.3%/day; p less than 0.01). The time required to return to hematocrits of 30% (9.9 vs. 17.4 days, p less than 0.001) and to baseline hematocrits (11.9 vs. 32.1 days, p less than 0.01) were both significantly shorter in the rHuEPO group. The data show that rHuEPO accelerates the recovery from anemia in the postoperative setting. Acceleration of erythropoiesis represents another alternative to homologous transfusion.(ABSTRACT TRUNCATED AT 250 WORDS)

Anemia↗
PubMed1989

Liposome-encapsulated hemoglobin as an artificial red blood cell: characterization and scale-up.

Encapsulation methods using high pressure extrusion and homogenization were developed which produce hemoglobin-containing liposomes, approximately one micron or less in diameter with an oxygen-carrying capacity of more than half that of red blood cells (RBCs). These methods were developed for scaling-up liposome-encapsulated hemoglobin (LEH) production. Previously, the lack of adequate scale-up methods has been a serious barrier to full scale efficacy and toxicity testing for all the researchers engaged in such investigations. The scale-up methods and characterization of the resulting LEH preparations are presented.

Blood Substitutes↗
PubMed1989

Perioperative recombinant human erythropoietin.

The risks of transfusion-associated infectious disease have made increased efforts to avoid homologous transfusion imperative. Little attention has been focused on efforts to accelerate erythropoiesis as a method of reducing homologous blood use. Recombinant human erythropoietin (rHuEPO) has been shown to enhance erythropoiesis. The purpose of this study was to evaluate the effects of perioperative rHuEPO administration on postoperative erythropoiesis. Fifteen baboons were divided into three groups of five each. Group I received no rHuEPO. Group II received five daily preoperative doses of rHuEPO (1000 U/kg). Group III received five daily preoperative doses and 14 daily postoperative doses of rHuEPO (1000 U/kg). All animals underwent a laparotomy followed by an exchange transfusion to a final hematocrit of 15%. The time in days required to recover to hematocrits of 20% was significantly shorter in both groups that received preoperative doses of rHuEPO when compared with that of controls (3.3 vs 5.7 days, p less than 0.01). The recovery times to hematocrits of 25%, 30%, and baseline levels were all significantly shorter in the group that received both preoperative and postoperative doses of rHuEPO. The data show that perioperative dosage of rHuEPO significantly accelerates postoperative erythropoiesis. Perioperative administration of rHuEPO may reduce the requirements for homologous transfusion.

Animals↗
PubMed1988

Coronary vascular actions of stroma-free hemoglobin preparations.

The left anterior descending coronary artery was cannulated in anesthetized, open-chest dogs for use as a coronary test bed to assess the coronary vascular actions of oxygenated, unmodified and pyridoxylated, partially cross-linked (polymerized), stroma-free hemoglobin solutions (SFHS). The actions of these SFHSs were assessed in this test bed, by comparison with perfusion with whole blood. Unmodified SFHS caused significant vasoconstriction, whereas pyridoxylated, partially polymerized SFHS did not do so. The existing coronary flow during perfusion with either SFHS preparation, under basal conditions, did not increase during intracoronary infusion of adenosine. Coronary flow-autoregulation was also altered during perfusion with either SFHS, because the "normal" reactive hyperemia response, observed in the control experiments, was not seen. These findings suggest that both unmodified and pyridoxylated cross-linked (70% polymers) hemoglobin preparations possess some vascular activity when tested in the canine coronary circulation.

Animals↗