P&T News: April 1994, Vol. 14, No. 10

Colloids Versus Crystalloids: Which Therapy Is Right?

Ray Hosek, M.D., R.Ph.
Peer Review Status: Internally Peer Reviewed by Peter Jebson, M.D., Director of Surgical Intensive Care Unit

The object of resuscitation in hypovolemia is to maintain perfusion to vital organs and to increase oxygen transport, as well as carriage of other vital substances.4 In principle, the less fluid necessary to achieve these objectives the better. With all intravenous fluids there is some loss of fluids and solute from the intravascular space into the interstitial space which subsequently has to be cleared by lymphatic drainage. Furthermore, there is a solute load with potential adverse effects that has to be cleared alter. To avoid fluid overload and its sequelae, replacement of fluids requires careful monitoring.5 These factors make careful selection of an appropriate fluid and its administration essential. Lastly, resuscitation must be tailored to the current and preexisting disease sates of the patient.

Plasma substitutes such as dextrin and albumin, having larger molecules than crystalloid or electrolytes solutions, are claimed to remain in the intravascular space longer and preserve higher levels of intravascular water.6,7

Such claims assert that colloids maintain blood volume longer than non-protein solutions. Other clinicians strongly support the contention that crystalloids have equal capability of raising intravascular volume, remain in the intravascular space long enough to be of practical value, and have other distinct advantages over colloids.8,9

These claims have led to a long-standing controversy over the relative merits of crystalloids and colloids.10 This conflict has not been resolved over the last 20 years despite the work of many researchers.8,11 The most desirable replacement solution is one that only increases plasma volume but also improves tissue oxygenation. Whole blood is a complete and physiologic volume expander.

However, some authors content that not all volume replacement needs are best met with protein containing solutions, and not all volume deficient situations require the same solution. For instance, Shoemaker suggests that elective surgical patients who are not critically ill can adequately be treated with crystalloid solutions.4 An understanding of the patient's physiological abnormalities contributes to appropriate selection of a resuscitation fluid. The goal of this article is to discuss the merits of the various resuscitation fluids, particularly the value of hetastarch as a resuscitation fluid in the appropriate surgical patient population.

Pathophysiology
The signs and symptoms of acute peripheral circulatory failure or shock depend on the degree of blood volume depletion, the duration of that depletion, and the ability of the body to compensate. Shock is a clinical syndrome representing acute perfusion failure and can be classified into four categories: hypovolemic, cardiogenic, distributive, and obstructive. Hypovolemic shock is due to a deficit of vascular volume following endogenous loss of blood, plasma, and/or electrolyte fluid. In addition, cardiogenic, distributive, and obstructive forms of shock often are complicated by absolute or relative hypovolemia.2 Although dehydration may result in hypovolemic shock, hemorrhage or internal loss of fluid are common causes of hypovolemia in the surgical patient. With the fall intravascular volume, there is diminished venous return to the right heart, low cardiac output, and a drop in systemic blood pressure. Mechanisms come into play to counteract the falling blood volume and blood pressure. Reflex sympathetic vasoconstriction initiates peripheral and splanchnic vasoconstriction and increased peripheral resistance to divert blood to the brain and coronary arteries. This shunting mechanism worsens perfusion to peripheral organs and promotes anaerobic metabolism, reflected in the progressive buildup of lactic acid. The peripheral vasoconstriction also causes impairment of renal function, manifested either as oliguria or anuria. In this serious amplification of shock, the volume of urine produced varies almost in direct proportion to the effectiveness of the compensatory mechanisms and therapy.12

Several mechanisms come into play to preserve a physiological state in acute circulatory failure. Cardiovascular signs are secondary to the decrease in plasma volume, and hypotension usually occurs if the fluid deficit is severe. It is known that severe volume depletion depresses all body systems.13 In elective or emergency surgery, the severity of the surgical procedure often determines the degree and type of fluid loss. In addition to blood loss from bleeding, there are extracellular fluid changes during major operations. Extracellular fluid sequestration is due to increased microvascular permeability with plasma and protein moving into the interstitium.11 One example of sequestration is accumulation of fluid into the peritoneal cavity which represents shifts in fluid distribution in the extracellular fluid space, but not truly lost from the body.

In the emergency resuscitation of trauma with shock, the primary problem is low intravascular volume while secondary problems involve expansion or contraction of the interstitium depending on the patient's fluid status. The majority of patients suffer from either relative or absolute blood deficits and an urgent need to replenish extracellular fluid volume. In the later stages of circulatory shock, the permeability of the capillaries gradually increases and large quantities of fluid move into the tissue space. This further decreases blood volume with a secondary fall in the cardiac output which makes tissue perfusion more severe. Under these dynamic circumstances, control of these interrelated clinical factors is difficult to obtain, and the clinician's evaluation of different fluid regimens becomes nearly impossible.4,14

General Description of Resuscitation Fluids
In the clinical setting, the physician has several crystalloid and colloid solutions available to manage fluid deficits: Ringer's lactate, 0.9% sodium chloride (normal saline), albumin, hetastarch and dextran. The advantages and disadvantages of crystalloid and colloid fluids are summarized in Table 1.

Table 1. Comparisons/Contrasts Among Various Crystalloid and Colloid Solutions
Name	Advantages	Disadvantages	Cost Comparison[1]	Toxicity Information	Dose/Rate of Administration
Ringer's Lactate	Inexpensive; readily available; reaction free	If excessive amount given without proper monitoring, can cause peripheral/pulmonary edema; excessive fluid often given (5 L may be needed for 1 L blood loss).	$0.85 for 1000 ml	During massive infusions, lactate may accumulate and worsen tissue acidosis or affect CNS in patients with hepatic failure, renal failure or shock.	Usual volume needed for resuscitation ranges from 6-10 L during 24 hour period.
0.9% Sodium Chloride	Inexpensive; readily available reaction free	If excessive amount given, causes peripheral/pulmonary edema; no protein to provide COP; excesive amounts needed for resuscitation.	$0.68 for 1000 ml	Larger quantities than colloids required for resuscitation in shock.	Usual volume needed for resuscitation ranges from 6-10 L during 24 hour period.
Albumin	Useful in acute volume depletion situations; less coagulopathies than hetastarch.	Expensive; short supplies possible; minor increases in PT, PTT, ACT.	$72 for 100 ml 25%	May bind calcium due to citrate content; may cause bleeding due to decrease platelet aggregation and dilution of coagulation factors and platelets.	Hypovolemic shock dose is 100-150 ml of 25% for adults; may repeat after 15-30 minutes.
Hetastarch	Less expensive than albumin; non-antigenic (no histamine release); blood supply not affecting availability; flexible plastic bag.	Contraindicated in Van Willebrands disease; limit to 1500 ml/day; bleeding due to hemodilution; circulatory and pulmonary overload possible.	$45 for 500 ml	Can cause liver dysfunction/ascites due to intrahepatic obstruction; has caused disseminated intravascular coagulation (DIC) and intracranial bleeding in patients with SAH.	Usual adult dose is 500-1000 ml; maximum dose is 1500 ml/day for 70 kg adult.
Dextran	Less coagulopathies than hetastarch.	Cannot be used in renal failure; coagulopathies due to hemodilution and decrease platelet adhesion; higher incidence of anaphylaxis than hetastarch.	$15 for 500 ml, dextran 40 $8 for 500 ml, dextran 70	With tissue diffusion, causes edema when capillary membrane integrity is disrupted. Promotes histamine release in humans to cause anaphylaxis.	Low molecular weight dose is not more than 1500 ml/day for adults. High molecular weight dose is not more than 1000 ml/day for adults.
[1] Refers to acquisition costs at The University of Iowa Hospitals and Clinics (March, 1994)

Crystalloid fluids are essentially isotonic with human plasma and contain sodium as the primary osmotically active particle. Ringer's lactate and normal saline distribute evenly throughout the extracellular space. In healthy adults, approximately one-fourth of the infused volume remains in the intravascular space after one hour. Equilibration with the extracellular space occurs within 20 to 30 minutes after infusion.14 In the critically ill patient, only one-fifth or less may remain in the circulation 1 to 2 hours after infusion.

Colloids are solutions which contain natural (albumin) or synthetic molecules (hetastarch or dextran) that are relatively impermeable to the vascular membrane.1 In man, albumin is produced in the liver and represents 50% of hepatic protein production. Albumin (molecular weight of 66,300 to 69,000) is the major plasma protein active in osmosis and is responsible for 80% of the plasma colloid oncotic pressure (COP). This protein distributes throughout the extracellular space, and it stays in the intravascular compartment longer than crystalloids since colloids are relatively impermeable to the vascular membrane. Albumin's plasma half-life is 16 hours. After two hours, 90% remains in the intravascular space. Albumin is most often used for its oncotic properties in the resuscitation of patients with an acutely diminished intravascular volume. Albumin may lower serum ionized calcium producing a negative inotropic effect on the myocardium and can cause minor changes in prothrombin time (PT), partial thromboplastin time (PTT), and activated clotting time (ACT), with platelet counts decreasing in critically ill patients. The incidence of albumin-induced anaphylaxis is between 0.47% and 1.53%.6,11 Albumin is commercially available as a 5% or 25% solution with isotonic saline as the carrier. When 100 ml of 25% albumin is infused, intravascular volume increases to 450 ml in 30 to 60 minutes.6

Hetastarch, a synthetic colloid derived from corn starch, is made of a heterogeneous group of molecules ranging in molecular weight from under 10,000 to over one million. This glucose polymer initially expands plasma volume by an amount equal to the volume infused. Plasma volume remains 70% expanded for three hours after the infusion with 84% of the molecules present in circulation at 10 minutes. Because of heterogeneity of the hetastarch molecule, its pharmacokinetic properties are complex. Its disappearance from the body is governed by the extent of hydroxyethylation and the molecular weight of the starch. Smaller molecules with molecular weights less than 50,000 will be readily excreted in urine; whereas, the larger molecule will undergo enzymatic degradation before elimination. Human data indicate at least 64% of hetastarch is eliminated after 8 days and 85% is cleared by 28 days; it has a biological half-life of 17 days.6 Hetastarch is indicated for use as a plasma volume expanding agent in shock from hemorrhage, trauma, sepsis, or burns. Hetastarch is associated with minor alternations in laboratory measurements. Coagulation profile discrepancies include a transient decrease in platelet count and prolonged prothrombin and partial thromboplastin times. In clinical studies to date, bleeding is a problem in only a small minority of cases.6 The incidence of anaphylactic reactions to hetastarch is less than 0.085%.6,11 Hetastarch is available as a 6% solution in 500 ml of 0.9% sodium chloride.14,15

Dextran solutions are glucose polymers fractionated to provide a low molecular weight and a higher molecular weight product. Dextran 70 has an average molecular weight of 70,000 and is used for plasma volume augmentation during resuscitation. High molecular weight dextran expands the plasma volume by an amount equal to 80% to 120% of the volume infused and the plasma volume is increased for up to 6 hours after infusion. Whereas, high molecular weight dextran is used for its plasma expanding properties, the main use of low molecular weight dextran, which has a molecular weight of 40,000, is as a priming solution for extra corporeal pump circulation in cardiac surgery. Dextrans can decrease platelet adhesiveness, serum fibrinogen, and other factor levels to cause bleeding. Dextrans promote histamine release and have been reported to cause anaphylaxis in 1% to 5.3% of cases.6,11 The half-life of these substances increase as the molecular weight rises. Dextrans which have a molecular weight exceeding 55,000 have a half-life exceeding 12 hours. Renal insufficiency (glomerular filtration rate less than 10 ml/minute) decreases the clearance of dextrans and increases half-life of low-molecular-weight dextran by a factor of 4 to 6. Also, dextran-induced renal failure can occur in the face of unrecognized hypovolemia.6 The volume of distribution is not altered by renal dysfunction, but dextrans can diffuse into tissues to cause edema when capillary membrane integrity is disrupted.

Clinical Trials of Resuscitation Fluids
As early as 1964, researchers were suggesting that patients with circulatory shock could be successfully resuscitated with either crystalloid or colloid solutions, provided that appropriate hemodynamic end-points were utilized.16-19 These studies were interesting in that they did not provide definitive hemodynamic monitoring guidelines. In the early 1980s, work by Rackow and Shoemaker, looking at colloids and crystalloids, found the resuscitation volume was 2 to 4 times larger with crystalloids than with colloids to produce an equivalent increase in plasma volume.16,20 Crystalloids are associated with a more transient blood volume increase due to the extravacular distribution of the infused fluids.21,22 The reported transient nature of crystalloid solutions has led many physicians to prefer colloid solutions. The decision is further complicated by the choice between albumin at a high cost versus the less-expensive, protein substitute, hetastarch. Evidence provided by Rackow suggests that of the commonly used colloidal solutions, 6% hetastarch is as effective as 5% albumin as a volume expander.16,23

Harpt and Rackow conducted a prospective study involving 26 patients with hypovolemic or septic shock showing that 6% hetastarch was as effective as 5% albumin as a replacement fluid, and the resuscitation with either fluid was associated with a lower incidence of pulmonary edema (22%) than resuscitation with 0.9% normal saline (87%). Two to four times the volume of normal saline was required to produce hemodynamic stability as compared to albumin or hetastarch.24

More recently, Puri et al compared hetastarch and albumin in 50 critically ill patients requiring replacement of intravascular fluid losses.25 The data showed that administration of hetastarch or albumin produced significant increases in pulmonary artery wedge pressure (PAWP), mean arterial pressure (MAP) and left ventricular stroke work index with decreases in systemic vascular resistance in both groups. These changes were not significantly different between groups with the exception of left ventricular stroke work index. Cardiac function improvement and oxygen delivery increases occurred in both groups at a comparable rate. Pulmonary vascular congestion developed or was aggravated in three hetastarch patients (12%) and four albumin patients (16%). The authors concluded that hetastarch was as effective as albumin in improving tissue perfusion, cardiac output and blood pressure; costs approximately 50% less than albumin; and usually does not impair coagulation to a clinically significant degree when dosed less than 20 ml/kg body weight.25

Dextran is an effective agent for plasma expansion as shown by Karanko.26 The effects of 4% plasma protein solution, 6% high molecular weight dextran, and 5% oxypolygelatin solution (not available in U.S.) were compared in postcardiotomy patients with normal ventricular function. similar, immediate increases in plasma volume were noted in all three groups; but one hour after infusion, the hemodynamic effects of dextran were superior to those of the other two solutions.26 However, as mentioned earlier, dextran does have some clinically important adverse effects.6,11

In reviewing the published literature, one concludes that no consensus has emerged as to whether one type of volume expander is superior to another in the setting of acute blood loss.11 Therefore, the physician is left to choose between the cheaper hetastarch versus the more expensive albumin (dextran is eliminated from consideration due to its anaphylactic potential). Since its introduction, hetastarch has been associated with coagulation concerns that have prompted the physician to assess the significance of bleeding with hetastarch. It alters coagulation in vivo through three dose-dependent mechanisms: fibrinolysis is accelerated; levels of factor VIII activity are reduced; and platelet coating decreases adhesion which can increase bleeding time.27 Falk and Puri showed that these effects were clinically insignificant at doses less than 1.2g/kg.28,29 Doses exceeding 2 g/kg are associated with clinical and laboratory test abnormalities that take as long as seven days to resolve. Despite these laboratory test abnormalities, large volumes of hetastarch, up to 15,000 ml/day, have not demonstrated local bleeding or systemic coagulopathy.28,30

Selection of the Most Appropriate Resuscitation Fluid
When the primary circulatory problem in shock is hypovolemia, therapy should be directed toward restoration of the blood volume with the ideal resuscitation fluid. The ideal fluid is one that can carry oxygen. The available crystalloid and colloid solutions are limited due to their inability to carry oxygen. Whole blood is a complete and physiological volume expander which is limited by its poor shelf life, fluctuations in stocks, risk of viral contamination, allergic reactions, and high cost.11,31 Although, crystalloid and colloid solutions can not carry oxygen, their usefulness is increased by their availability and relative low risk of infection.

Hemodynamic resuscitation is likely to be accomplished more rapidly with colloids since colloid solutions expand vascular volume with less fluid than crystalloid solutions. Crystalloid solutions equilibrate across the vascular membrane such that one-tenth to one-quarter of the solution remains in the plasma at the end of the infusion. Crystalloid solutions also dilute plasma proteins with consequent reduction in colloid osmotic pressure which allows for the filtration of fluid into the interstitial. Crystalloid fluid resuscitation may result in excessive salt and water administration leading to interstitial edema.

With these effects in mind, if the goal in fluid therpay is to replenish interstitial dehydration, then crystalloid solutions would be the treatment of choice.33 If the goal in resuscitation is to increase the plasma oncotic pressure and effectively move fluid from the interstitial compartment into the plasma compartment, then the clinician can select a colloid solution.31 Advantages of hetastarch over other synthetic colloid solutions include a lower incidence of side effects and allergic reactions, stability upon prolonged storage, immediate availability, no dependence on human blood donation, no risk of serum-transmitted diseases, and lower cost.33,34 Hetastarch produces physiological effects comparable to dextran and clinical studies have indicated that hetastarch is at least as effective as dextran as a plasma expander.35-37 High molecular weight dextrans do not seem more likely to cause bleeding than hetastarch when recommended doses are used, but dextrans do promote histamine release (hetastarch does not)_ which can cause anaphylactoid reactions.31

Conclusions
Based on the available informatio9n, in the non-critically ill patient crystalloid solutions usually provide adequate replacement therapy. In patients with shock, it appears colloid solutions are a better alternative to massive infusion of crystalloids since they restore plasma volume without the excessive salt and water administration that can lead to over-expanded interstitial water and pulmonary edema.38 If the choice is which colloid to use in a hypovolemic patient and if side effects are not the issue in the surgical patient, then the literature would support the use of hetastarch over albumin since they exert similar plasma expanding properties.6 This logic would seem to also justify the use of hetastarch over albumin when the clinical need is for only one unit of a plasma expander. The general guidelines where hetastarch can be used in pace of albumin as a plasma expander are summarized in Table 2.

Table 2. General Guidelines for the Use of Hetastarch and Albumin

Hetastarch can be used for: Hypovolemia due to blood loss accompanied by classical signs such as hypotension, tachycardia, etc. Hypovolemia due to thermal injury involving more than 30% BSA with second or third degree burns Plasma volume expander after cardiopulmonary bypass Replacement when only one unit of plasma volume expander is needed Albumin should be used in patients with: Severe bleeding disorders (i.e., patients with Von Willebrand's disease) Severe congestive heart failure (i.e., Class 3 or 4) Known hypersxensitivity to hetastarch Acute liver failure Cerebral vasospasm associated with subarachnoid hemorrhage Increased risk of intracranial hemorrhage NOTE: The maximum recommended dose of hetastarch in a 24 hour period is 1500 ml (3 units). High daily dosages have been associated with coagulation disorders, slight prolongation of PT and PTT clotting times, transient decrease in platelet counts and fibrinogen levels, and mild temperature elevations, chills, itching, and influenza-like symptoms. Albumin or plasma protein fraction can be given if the patient requires further colloid therapy after the first three units of hetastarch. ______ Approved by Pharmacy and Therapeutics Subcommittee November 1991, revised December 1992.

References

1. New Horizona. 1993;1:127-36.

2. Textbook of Surgery. Philadelphia: WB Saunders;1992:11-2.

3. Ann Surg. 1961;154:803.

4. J Surg. 1981;142:73-84.

5. J Cardiothor Anes. 1988;2(Suppl):24-32.

6. Pharmacologic Approach to the Critically Ill Patient. Baltimore: Williams & Wilkins; 1988:219-40.

7. Surg Gyn Obstet. 1978;146:97-104.

8. Surgery. 1989;105:65-71.

9. Conn Med. 1986;50:689-91.

10. J Surg. 1981;142:73.

11. Clin Pharm. 1993;12:415-28.

12. Pathologic Bassi of Disease. Philadelphia: WB Saunders;1974:345-52.

13. Textbok of Surgery. Philadelphia: WB Saunders;1992:27.

14. J Cardiothor Anes. 1988;3(Suppl):13-23.

15. DuPont Pharma Hespan (Hetastarch) Package Insert. Wilimington, DE:1992 October.

16. Cirt Care Med. 1983;11:839-50.

17. Arch Surg. 1964-88:688-93.

18. Surgery. 1979;85:129-39.

19. Surgery. 1981;89:434-8.

20. Am J Surg. 1981;142:73-84.

21. Resusc. 1976;5:85-92.

22. Crit Care Med. 1976;4:71-8.

23. Crit Care Med. 1983;11:518-23.

24. Crit Care Med. 1982;10:159-62.

25. Crit Care Med. 1981;9:833-7.

26. Cirt Care Med. 1987;15:1015-22.

27. Intern Care Med. 1985;11:300-6.

28. J Clin Pharmacol. 1988;28:412-5.

29. Crit Care Med. 1982;10:229. Abstract.

30. Arch Surg. 1983;118:804-9.

31. Clin Pharm. 1993;12:335-46.

32. Chicago Crit Care Met. 1993;12:248-50.

33. Br J Anes. 1973;45:958-62.

34. J Burn Care Rehab. 1989;10:11-6.

35. Surg Gyn Obstet. 1970;131:255-67.

36. Anaesthesist. 1975;24:193-7.

37. Acta Anes Scand. 1984;28:595-9.

38. Textbook of Critical Care Medicine. Philadelphia: WB Saunders;1984:624-5.

Adverse Drug Reaction Reports

Ranitidine - Mental Status Changes
A 67-year-old female was admitted for evaluation of her three-month history of abdominal pain, weight loss, and diarrhea. She had no prior psychiatric history. Endoscopic evaluation revealed an ulcerated gastroesophageal junction, gastritis, and multiple ulcerations of the duodenum, suggestive of Zollinger-Ellison syndrome. Further evaluation documented abnormally high levels of gastrin and a positive secretin test.

Ranitidine therpay was initiated and continued for nine days with gradually increasing doses. After 36 hours of intravenous ranitidine 100 mg every 6 hours, the patient began to exhibit signs of delirium. She became anxious and experienced gross muscle fasciculation in all extremities. She became disoriented to time and place, both recent and remote memory were impaired, and she developed persecutory ideas that hospital staff would harm her. Her delirium was considered to be most likely drug-related. Ranitidine was stopped and the patient was placed on omeprazole 120 mg daily. Within 24 hours of stopping ranitidine, her confusion lessened and her fasciculations stopped. By 72 hours after the discontinuation of ranitidine, her sensorium completely cleared.

Three days later, she underwent resection of a gastrinoma in her duodenum. Because of the need for intravenous therapy for high levels of gastric acid output, she was again placed on ranitidine 50 mg every eight hours. She was also receiving epidural morphine. The patient experienced elevated gastric output from her nasogastric tube and ranitidine was increased on the third post-operative day to 100 mg every eight hours. Within 24 hours of that increase, she again became confused, disoriented, experienced memory impairment, and had persecutory ideas. Ranitidine was reduced to 50 mg every eight hours and the patient's symptoms diminished somewhat. The next day she resumed oral omeprazole therapy and her ranitidine was stopped. Over the next two days her confusion continued to diminish and she again returned to her baseline sensorium of completely intact cognitive function.

Abstracted from: Eisendrath SJ, Ostroff JW. Ranitidine-Associated Delirium. Psychosomatics 1990;31:98-100.

Like cimetidine, ranitidine has been shown to cause reversible mental status changes such as: confusion, agitation, depression, and hallucinations. The manufacturer of ranitidine states these effects are rare, occurring predominantly in severely ill, elderly patients.

Ranitidine doses should be reduced in elder patients or when renal impairment is present. In addition, patients should be observed for potential mental status changes. The initial ranitidine dosing recommendations are as follows:

CrCl less than 50 ml/min, 150 mg orally every 24 hours or 50 mg parenterally every 18 to 24 hours. The frequency of dosing may be increased to every 12 hours with caution.

Increased awareness of adverse drug reactions can assist the clinician in differential diagnosis of medical problems and events.

Pharmacy and Therapeutic

Drugs Added to Stock

GABAPENTIN Capsules: 100 mg, 300 mg, 400 mg Gabapentin (Neurontin® - Parke-Davis) is an anticonvulsant indicated as adjunctive therapy in the treatment of partial seizure with and without generalizations in adults

APROTININ Injection: 10,000 Kallikrien Inhibitor Units per ml, 100 ml and 200 ml vials Aprotinin (Trasylol® - Miles) is a protease inhibitor that is indicated for prophylactic use to reduce perioperative blood loss and the need for blood transfusions in patients undergoing cardiopulmonary bypass surgery. NOTE: The use of aprotinin is restricted Cardiothoracic Surgery.

ZOLPIDEM Tablets: 5 mg, 10 mg Zolpidem (Ambien® - Searle) is a nonbenzodiazepine hypnotic.

MULTIVITAMINS WITH ZINC PEDIATRIC DROPS Oral Liquid Multivitamins with zinc pediatric drops (ADEKs® Pediatric Drops - Scandipharm) are formulated to meet the needs of infants and children with malabsorption conditions. Each ml contains: Vitamin A (palmitate) 450 mg, Vitamin D (cholecalciferol) 10 mcg, Vitamin E (delta-alpha tocopheryl) 27 mg, Vitamin K (phytonadione) 0.1 mg, Vitamin C (ascorbic acid) 45 mg, Thiamin (Vitamin B1) 0.5 mg, Riboflavin (Vitamin B2) 0.6 mg, Niacin (niacinamide) 6 mg, Vitamin B6 (pyridoxine) 0.6 mg, vitamin B12 4 mcg, Biotin 15 mcg, Pantothenic Acid (d-pantothenol) 3 mg, Zinc (as sulfate) 5 mg, beta Carotene 1 mg

TIMOLOL Ophthalmic Gel Forming Solution: 0.25%, 0.5% Timolol gel forming ophthalmic solution (Timoptic® XE - MSD) is indicated for the once-a-day management of glaucoma.

LEVOCABASTINE Ophthalmic Suspension: 0.5% Levocabastine ophthalmic solution (Livostin® - Iolab) is a selective H1-receptor antagonist indicated for the temporary relief of seasonal allergic conjunctivitis.

CALCIPOTRIENE Ointment: 0.005% Calcipotriene (Dovonex® - Westwood) is a synthetic vitamin D derivative that is indicated for the treatment of moderate plaque psoriasis.

ESTRADIOL Tablets: 2 mg Estradiol (Estrace® - Mead Johnson) tablets are indicated for estrogen replacement therapy.

Drugs Deleted from Stock

BUPIVACAINE 0.5% with EPINEPHRINE 1:200,000 INJECTION, 5 ML AMPUL (Sensorcaine® Test). Bupivacaine 0.5% with Epinephrine 1:200,000 injection in a 30 ml ampul is available.

CHLOROTRIANISENE CAPSULES (Tace®). Diethylstilbesterol tables are available.

EPINEPHRINE 1:1000 INJECTION, 1 ML SYRINGE. Epinephrine 1:1000 injection 0.2 ml syringe (Epi-Pen®) is still available.

IODIPAMIDE MEGLUMINE 52% INJECTION (Cholografin®). Other radiopaque media are available.

ISOXSUPRINE TABLETS (Vasodilan®). Cyclandelate tablets are available.

LIDOCAINE 2% WITH 1:50,000 EPINEPHRINE INJECTION, 1.8 ml cartridge. Lidocaine 2% with 1:100,000 Epinephrine injection, 1.8 ml cartridge is available.

LYPRESSIN NASAL SPRAY (Diapid®). Desmopressin nasal solution and spray (DDAVP) are available.

METHANTHELINE CAPSULES (Banthine®). Propantheline tablets are available.

MITOTANE TABLETS (Lysodren®).

NIACINAMIDE TABLETS. Niacin tablets are available.

PENTOBARBITAL ELIXIR. Pentobarbital injection and suppositories are available.

POTASSIUM CHLORIDE 20 mEq SUSTAINED-RELEASE TABLETS (K-Dur®). Potassium chloride 8 mEq and 10 mEq sustained-release tablets capsules are available.

SODIUM CHLORIDE 2% OPHTHALMIC SOLUTION (Adsorbonac®). Sodium Chloride 5% ophthalmic solution is available.

THIOPENTAL RECTAL SOLUTION (Pentothal®). Propofol and other anesthetic agents are available.

TRIAMCINOLONE 2.5 mg/ml with LIDOCAINE 0.375% INJECTION. Triamcinolone 5 mg/ml injection is available.

TRIAMCINOLONE TABLETS. Prednisone, Hydrocortisone, and Dexamethasone tablets are available.

WRIGHT'S BLOOD STAIN.

Additional Actions

HYDROCORTISONE INJECTION The Pharmacy and Therapeutics Subcommittee considers the two water-soluble salts of hydrocortisone injection - hydrocortisone sodium succinate and hydrocortisone sodium phosphate - to be therapeutically equivalent and may be used interchangeably, except in the cases where a preservative-free product is required. When a preservative-free product is required, the hydrocortisone sodium succinate product will be dispensed. Therefore, as per Subcommittee action, the least expensive drug will be stocked for general use.

ORAL POTASSIUM CHLORIDE SUSTAINED-RELEASE PREPARATIONS The Pharmacy and Therapeutics Subcommittee considers the wax matrix and microencapsulated formulations of oral sustained release potassium chloride to be therapeutically equivalent and may be used interchangeably.

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