The use of LIS for blood usage review. Experience in a children's hospital.

To comply with the requirements of the Joint Commission for the Accreditation of Healthcare Organizations (JCAHO) and to facilitate the review process, the authors designed a program to screen for the appropriateness of packed red cell (PRC) and platelet concentrate (PLT) transfusions. The purpose of this report is to describe the methodology of the review process. A quality assurance (QA) monitor was created in the Laboratory Information System (LIS) to screen indicators: hemoglobin for PRCs and platelet count for PLTs. Numerical value limits were defined to determine acceptable ranges. Each week, the LIS compiles a list of all patients who received transfusions and for whom the QA monitor determined that the values of the screened indicators were outside the defined appropriate limits. A detailed transfusion record is generated for each patient identified. During a six-month evaluation of this program, a total of 1,788 PRC and 3,109 PLT units were transfused. Of these, 582 PRC (32.5%) and 2,219 PLT (71.4%) units were within the acceptable guidelines. Lists for the remaining 1,206 PRCs and 890 PLTs were generated. Review of the transfusion record and other laboratory values from the LIS established the appropriateness of 1,052 PRC and 782 PLT transfusions. At the conclusion of the six-month period, the medical charts for 181 (11%) PRC and 108 (4.5%) PLT transfusions required chart review. This method provided major reduction in time of the transfusion review process. Similar guidelines may be used to monitor other transfusion products such as fresh frozen plasma.

Effect of the vasodilator peptides calcitonin gene-related peptide and atriopeptin on rabbit microvascular blood flow. Preliminary communication.

A neuropeptide known as calcitonin gene-related peptide (CGRP) has been shown to have vasodilatory properties in the rabbit epigastric island flap of almost equivalent potency to prostacyclin. The latter is currently regarded as the most potent vasodilator yet to be isolated. CGRP, with its longer-lasting effect in blood and its ability to overcome noradrenaline-induced vasospasm, may be promising for use during or after ischaemic flap transfer or replantation. Another known vasodilatory peptide, atriopeptin, was not as potent in the microvascular bed of the cutaneous flap as in major blood vessels.

The salvage of rabbit ischaemic epigastric free flaps using the vasodilator calcitonin gene-related peptide.

The rabbit epigastric free flap, subjected to 21 hours of warm (25 degrees C) ischaemia, was used as an experimental model to test the ability of two endothelium-dependent vasodilators, calcitonin gene-related peptide (CGRP) and carbamyl beta-methylcholine chloride (MCh, bethanechol chloride, the stable acetylcholine analogue) to improve flap viability. After the period of ischaemia, flaps were infused intra-arterially with either Hanks balanced salt solution (controls), CGRP or MCh for 30 minutes, and received additional intravenous boluses of these drugs at 2 and 32 minutes after revascularisation. The area of flap surviving improved significantly (p less than 0.025) from 39.9% (n = 18) for controls to 70.2% (n = 14) for CGRP treatment at 2 micrograms/kg, but was unchanged at 47.1% (n = 14) for MCh treatment at 50 micrograms/kg. Both CGRP and MCh significantly increased blood flow (p less than 0.05) resulting in 34% lower peripheral resistances compared with controls. These results suggest that CGRP has considerable clinical potential for the salvage of ischaemic flaps. CGRP must have several, as yet undefined, beneficial effects on the ischaemic tissue, since MCh invoked a vasodilatory response but failed to salvage ischaemic flaps.

Experience with calcium antagonists nitrendipine, diltiazem, and verapamil and beta 2-agonist salbutamol in salvaging ischemic skin flaps in rabbits.

This study investigated the efficacy of selected agents in the salvage of experimental skin flaps in rabbits after 21 hours of 25 degrees C ischemia. Calcium channel antagonists nitrendipine, diltiazem, and verapamil increased ischemic skin flap survival in rabbits from 33.3% for buffered saline infused controls to 71.4% (P less than 0.05), 71.4% (P less than 0.05), and 50.0% (not significant) respectively. The beta 2-adrenoceptor agonist salbutamol produced an increase in survival to 64.3%, which narrowly missed statistical significance. All four test agents invoked a vasodilatory response (greatest for nitrendipine, diltiazem, and salbutamol), a slight fall in blood pressure, and a small increase in heart rate. It is concluded that the vasodilatory response in the microcirculation of the ischemic flap helped to minimize the risk of occlusion due to thrombosis or cell sludging during reperfusion, thus leading to improved flap survival.

Prostacyclin and prostanoid modifiers aid ischemic skin flap survival.

Prostacyclin, the stable prostacyclin analogue carbacyclin, the thromboxane synthetase inhibitor UK-38,485, and the phosphodiesterase inhibitor dipyridamole were tested on rabbit epigastric free flaps for their ability to improve flap survival after a period of ischemia. Control flaps infused with a balanced salt solution had a 39.9% survival, whereas prostacyclin, carbacyclin, and dipyridamole significantly increased flap survival to 68.4% (P less than 0.05), 66.4% (P less than 0.05), and 66.9% (P less than 0.05), respectively. UK-38,485 improved survival slightly to 47.6% although not significantly. The improved flap survival correlated with the vasodilatory properties of the three successful agents whereas the antithrombotic properties of UK-38,485 were not sufficient, on their own, to increase flap survival.

A biochemical study of acute ischemia in rodent skin free flaps with and without prior elevation.

Elevation of a vascular island flap 24 hours before an ischemic insult (prior elevation) has been shown to significantly increase flap survival, and to decrease blood thromboxane levels, compared with acutely ischemic flaps. The current study considered whether prior elevation causes other biochemical alterations that could be beneficial for flap survival. Tissue levels of adenosine triphosphate (a major tissue energy store), superoxide dismutase (a major defense against free radicals), xanthine oxidase (an enzymatic source of free radicals), and edema were measured. Rat epigastric flaps, with or without prior elevation, had 10 or 12 hours of acute ischemia. Biopsies were taken at 0, 12, or 24 hours after reperfusion. Skin from flaps with no ischemia (control flaps) or control skin was harvested at the same times. Acutely ischemic flaps had significantly lower levels of adenosine triphosphate and less edema than those in prior elevated ischemic flaps after 12 hours of ischemia (both, p less than 0.05). Superoxide dismutase and xanthine oxidase did not vary significantly. It is not clear whether the increased adenosine triphosphate level in prior elevated flaps is the cause or the result of increased tissue viability. Prior elevation did not alter free radical mechanisms. Furthermore, prior elevation was beneficial for flap survival despite increased edema.

The redistribution of collagen in expanded pig skin.

Silicone tissue expanders were inserted subcutaneously in the buttocks of nine young pigs and gradually inflated to maximum capacity over 5 weeks. On the control side the expanders were left uninflated. Island buttock flaps were then raised, the expanders removed and the flaps spread into the same sites for 10 days. The tissue was harvested. Area measurements and full thickness skin biopsies were taken 10 days after flap inset in order to study the changes in collagen composition and isotypes in the skin layers. Ten days after inset of the flap the expanded skin had a mean 47% increase in surface area, was 9% thinner (from surface to implant), mostly due to thinning of the subcutaneous zone, but was not significantly different in water content, relative to the control skin. The expanded skin had a significant 9.3% increase (p less than 0.01, t test) in collagen content of the dermis. The relative proportions of Types I and III were not significantly changed by skin expansion in either the dermal/epidermal or subcutaneous/capsular zones. It is speculated that tensile factors during expansion stimulate the biosynthetic activity and/or mitotic activity of fibroblasts in the dermis to produce this gain in collagen in the expanded compared with unexpanded tissue.

Factors involved in salvaging ischaemic rabbit skin flaps: ATP and free radicals but not thromboxane.

Rabbit epigastric free flaps were subjected to ischaemia at 25 degrees C for 24 hours. At the time of revascularisation the flaps were infused intra-arterially with one of the following: Hanks balanced salt solution (control), the high energy phosphates PEP/ATP, the thromboxane synthetase inhibitor dazoxiben hydrochloride, the free radical scavenger SOD and a combination of all these agents (treated groups). Control ischaemic flap survival at post-ischaemia day 7 was 23.5%, while the other treatments resulted in improved flap survival of 43.5% (p less than 0.025), 23.5% (not significant), 38.6% (p less than 0.05) and 35.7% (p less than 0.05) respectively. None of these agents improved post-ischaemic blood flow significantly. These results would support the use of PEP/ATP or SOD in the clinical treatment of failing ischaemic skin flaps but do not support the use of dazoxiben hydrochloride.

The biochemical basis of secondary ischemia.

In this study rat epigastric island flaps were used as a model to investigate selected tissue biochemical changes occurring during secondary ischemia. It was hypothesized that free radical damage, depletion of free radical scavengers, depletion of ATP, and increased edema might explain differences in flap survival between partial (venous obstruction) and total (arteriovenous obstruction) ischemia and decreased flap survival with increasing ischemia time. Flaps were given 2 hr or primary ischemia, 8 hr of normal perfusion, then secondary ischemia of 0, 2, 4, 8, or 12 hr with either arteriovenous obstruction or venous obstruction. Biochemical analysis of the skin was performed after 0, 24, or 96 hr reperfusion. Only minor differences were found between arteriovenous and venous ischemia for any of five biochemical parameters, despite a previous finding that venous ischemic flaps are more susceptible to necrosis. Levels of xanthine oxidase and malonyldialdehyde (both indices of free radical generation) increased with ischemia time. Levels of superoxide dismutase (a free radical scavenger) correspondingly decreased. Tissue levels of ATP decreased after ischemia and recovered to normal for shorter but not for longer ischemia times after 96 hr of reperfusion in parallel with flap survival. Edema increased immediately after the ischemic insult but decreased once the tissue became necrotic. These results imply roles for free radicals, ATP, and edema in secondary ischemia, but do not distinguish between arteriovenous and venous secondary ischemia.

Coumarin and 7-hydroxycoumarin treatment of canine obstructive lymphoedema.

1. Canine obstructive lymphoedema was created in one hind leg of 30 dogs by irradiation of the groin and surgical removal of surviving lymph glands and lymphatics. The opposite leg served as a control. Once the oedema had stabilized, groups of 10 dogs were treated orally with 12.5 mg day-1 kg-1 for 8 months with either one of the benzopyrones coumarin (2H-1-benzopyran-2-one) and 7-hydroxycoumarin (7-hydroxy-2H-1-benzopyran-2-one), or placebo. 2. The two benzopyrones significantly (P less than 0.01) but gradually reduced the oedema by 20-30% over 8 months, as judged by circumferential measurements of the oedematous and control limbs. There was no change with the placebo. 3. In the oedematous fluids (lymph and interstitial fluid), benzopyrone treatment reduced the protein content and increased acid and neutral proteinase activity compared with the control limbs, while the levels of the proteinase inhibitor alpha 2-macroglobulin remained unchanged. Furthermore, these active drugs reduced the excess water content, thickness and hydroxyproline content of skin biopsies from oedematous limbs compared with those from control limbs. No changes were observed for the placebo group. 4. These biochemical changes suggest that benzopyrones can reduce the excess proteinaceous fluid in lymphoedema by increasing the levels of proteinase activity relative to the number of proteinase inhibitors. As a secondary event the amount of fibrosis in the skin is also reduced, presumably by an increase in collagenase activity from the mononuclear phagocytes. 5. These results support the hypothesis that benzopyrones activate the production of proteinases by mononuclear phagocytes.(ABSTRACT TRUNCATED AT 250 WORDS)

Effect of phosphoenolpyruvate and adenosine triphosphate on rabbit skeletal muscle after ischaemia: preliminary biochemical study.

The present study examined the effect of phosphoenolpyruvate (PEP) and adenosine triphosphate (ATP) on rabbit skeletal muscle flap survival after warm ischaemia. Two muscle flap models, rectus femoris pedicle flap and latissimus dorsi free flap, were subjected to a total ischaemia of 4 hours at 37 degrees C and 20 degrees C, respectively. Immediately prior to revascularisation, the muscles were infused with either Hanks' balanced salt solution (BSS) or Hanks' BSS containing 200 mumol PEP and 6.6 mumol ATP. Quantification of muscle damage was determined by measuring the plasma levels of creatinine kinase (CK), lactate dehydrogenase (LDH), lactate, potassium, and phosphate at 0, 2, 24, and 96 hours after revascularisation. Infusion of PEP/ATP compared with Hanks' BSS alone significantly decreased the efflux of CK in both rectus femoris (P less than 0.025) and latissimus dorsi muscles (P less than 0.05) and of LDH in the rectus femoris muscle (P less than 0.01). No significant changes were observed, however, for the plasma levels of lactate, potassium, and phosphate. From this study it was concluded that PEP and ATP partially protect skeletal muscle from ischaemia and reperfusion injury.

Protein metabolism and fibrosis in experimental canine obstructive lymphedema.

Obstructive lymphedema is a pathologic condition resulting in the accumulation and stagnation of serum proteins in the lymphatics and interstitial spaces. In a canine model of obstructive lymphedema, one limb was rendered lymphedematous, and various biochemical parameters were determined in this and an unaffected control limb. Both lymph and interstitial fluid had significantly decreased acid proteinase activity (comprising mostly cathepsin D-like enzymes) and neutral proteinase activity (comprising metallo, sulfhydryl, and serine proteinases, and collagenase). Possible reasons for these decreases could be: (1) saturation of macrophages and their surrounding environment with whole or partially digested proteins, or (2) elevation in the levels of circulating inhibitors like alpha 2-macroglobulin. The lymphedematous skin was significantly thicker than control skin and had elevated levels of collagen. However, unlike some fibrotic conditions, the relative proportions of types I, III, and V collagen, as determined by pepsin solubilization and neutral salt fractionation of the collagen fibrils, were similar to those found in normal skin. It is speculated that a decrease in the breakdown of collagen by collagenase and a continuing synthesis of collagen by fibroblasts led to an imbalance in favor of collagen deposition in the skin.