Bloodless Medicine Reports

Abstract

Bloodless surgery was introduced initially for the care of patients who refused blood transfusion. Recently however, adverse outcome with blood transfusion has been reported in virtually all subspecialties of surgery and conversely, improved outcome with non-transfusion surgery. Thus blood conservation is the standard of care because it is evidence-based. Thyroid surgery is historically associated with blood loss, and a lower hemato- crit would be expected postoperatively. We report a case of subtotal thyroidectomy for a large simple multinodular goiter using planned blood-conservation techniques tailored to the patient that resulted in maintenance of a normal hematocrit throughout the perioperative period. The patient received oral hematinics preoperatively, while acute normo- volemic hemodilution and other techniques were used to minimize intraoperative blood loss. The outcome was an optimized hematocrit preoperatively, minimal blood loss intraoperatively, and hematocrit which remained optimal on the third postoperative day and 3 weeks postoperatively. No allogeneic blood was used at any stage. This suggests that maintenance of normal hematocrit can be regarded as an achievable goal in high-risk surgery through blood-conservation techniques. Avoid- ing allogeneic blood transfusion is possible in a resource-poor setting, where HIV prevalence is high and screening of blood may be suboptimal, and it is the ideal clinical approach as demonstrated in this case report.

Introduction

The following is the methodology I use for the administration of intravenous iron dextran, for total dose infusion.  I have used this method for more than thirty-five years and it has worked quite well, with uniformly safe outcomes. During this time my patients have experienced allergic reactions far less often than one per hundred infusions, and none of these reactions has been a serious adverse event, and no instance of anaphylaxis has occurred.  Attached to this memorandum is a copy of a package insert for iron dextran (Infed). A current package insert for the iron dextran product being used should always be reviewed, since these package inserts are periodically updated, and the product is currently made by more than one manufacturer.

The administration of iron dextran should always be done under controlled conditions, with frequent monitoring of the patient’s vital signs, especially during the first ½ hour of administration, and every two hours or so after that.  Resuscitative equipment and medication, particularly epinephrine, should be available at the time of infusion. I am, however, pleased to report that in my more than 35 years of clinical use, having administered iron dextran to more than 2,500 patients, none of my patients has ever had a serious adverse event, required epinephrine treatment, or required hospitalization or acute medical care following an iron dextran infusion.

I use a method called Total Dose Infusion (TDI), wherein the total calculated replacement dose of iron is administered in a single, 4-hour infusion.  This method gives no more risk than giving a smaller dose of iron dextran (or any other intravenous iron salt), but neither does it confer more safety per dose.  It does, however, allow the patient to receive a single dose of intravenous iron rather than multiple doses of iron, and thus the net risk for IV iron is vastly reduced.  This is because anaphylaxis is not a dose related event, but rather a hypersensitivity phenomenon, and decreasing the number of antigenic exposures results in fewer risks of generating drug sensitization.    

Although iron dextran is approved for intramuscular administration, there have been reports in the medical literature of development of sarcoma or other malignancy in the vicinity of such injections, so I do not use intramuscular iron dextran.

The FDA has approved iron dextran for a maximal amount of 100 mg daily.  Thus, TDI is an off-label use of iron dextran.

Protocol and Technique for Total Dose Infusion of Iron Dextran

An intravenous line is started, using an intravenous catheter.   A 20 gauge catheter or larger is preferred. The smallest size to be used should be 22 gauge.  The intravenous solution to be used is normal saline.

DEXTROSE AND WATER SHOULD NEVER BE USED TO ADMINISTER IRON DEXTRAN!  

The frequency of adverse reactions is substantially higher when D5W is used instead of normal saline.  My volume of preference for the infusion is 500 cc. A large drip chamber (Buretrol brand) is connected to the IV bag and 100cc of saline is allowed into the drip chamber and the IV flow is begun, at 125 cc/hr.  An IV pump may be used here for convenience, but is not required. When it is clear that the IV line is functioning, the full dose of iron dextran is added to the IV bag via the medication addition port, and mixed with the saline.  One to two drops of the diluted iron dextran is then allowed to enter the large drip chamber. For an iron dextran dose of 3000 mg, the resulting concentration of iron dextran in the drip chamber would now be <0.008mg/cc, but as yet no iron dextran will have reached the patient.  The IV rate will carry some of the iron dextran to the patient within 2 to 5 minutes. This is effectively a “test dose.” If no change in vital signs occurs then gradually add additional iron dextran solution to the drip chamber over 10 to 15 minutes. There will be a continuing increase in the concentration of the solution reaching the patient, until finally the patient is receiving the full strength of the preparation (which is approximately 6.0mg/cc).  A recommendation from the literature for maximal safe rate of infusion is 12.5mg/minute, which would cap the administration rate at 2.08cc/min = 125cc/hr. No data for this recommendation are cited, and I frequently exceed this recommended maximum rate by administering the solution at a rate of 150 to 180 cc/hr. (=300 to 375mg/hr. = 15 to 18 mg/hr). If at anytime during the infusion the patient has any symptoms, I will slow the rate of infusion to a more tolerable rate, and proceed with the infusion.  For the rare patient with nausea or any suggestion of sensitivity to the infusion, I will at this time treat with diphenhydramine and/or glucocorticosteroid.  I do not routinely pretreat the patient with medications to prevent symptoms unless the patient has had symptoms from a previous iron dextran infusion.

The obvious benefit for this “test dose/rapid desensitization” method is to allow the patient to begin with a miniscule dose of iron dextran, rather than the package insert recommended 25mg, dose, which is sufficient to precipitate full-blown anaphylaxis if the patient is indeed sensitive.  The tiny dose gives an opportunity for the patient to have a smaller reaction and for the medical personnel to stop the infusion quickly, before the adverse reaction can fully develop.    On occasion, I have needed to slow an infusion, but none of my patients was unable to complete the full infusion, and no “medical resuscitation” beyond diphenhydramine and prednisone or dexamethasone has ever been required.

Care should be taken to avoid extravasation of the iron solution since it does stain tissue, although not permanently.  To decrease the risk of tissue staining, I request that the IV line be flushed with 20 cc of normal saline at the end of the infusion in order to minimize the presence of any residual iron dextran in the iv catheter.

The patient should be forewarned of two other small concerns.  Particularly with higher doses of iron dextran, perhaps as many as 1 in 3 patients may experience a few days of achiness after the infusion.  This is self-limited, and rarely lasts beyond a few days. Fair-skinned patients may note the appearance of a mild “sun-tan” for a few weeks after the iron dextran, again, more so with higher doses, due to temporary localization of some of the iron dextran in the skin.

A brisk reticulocytosis often occurs starting a few days after the infusion.  The rate of red cell production and hemoglobin rise is generally proportionate to the severity of the patient’s anemia:  most patients with severe iron deficiency will show a hemoglobin rise of approximately ½ gram/day for a week (i.e. 3 to 4 gram rise in hemoglobin in one week) if there are no other complicating medical problems.  Patients with a lesser deficit, or with complicating illnesses will have a slower rate of rise.

Dose calculation for the iron dextran using the package insert is clumsy and requires that the physician use the supplied table.  I find it much simpler to do the following dose calculation: simply multiply the deficit for the hemoglobin (in grams) by 250mg (amount needed to form a pint of blood), and add an additional 1000 mg to replace the normal reserve amount.  Thus, a 17 year old girl with iron deficiency from menometrorrhagia, with a hgb of 5 and ferritin of 3, should receive 7 (hgb deficit in grams) X 250 mg of iron dextran = 1750 mg, for deficit replacement, plus 1000 mg for replenishment of normal iron reserves = 2750 mg for total dose.  This would be given in 500 cc normal saline, IV over 4 hours.

Abstract

In primary or first time cardiac surgery, it takes just several minutes for the surgeon to open the chest by median sternotomy (cutting the breast bone). The anatomic landmarks are intact, which allows the surgeon to perform the heart operation without a lot of difficulty. In fact, many operations have been performed without blood transfusion. Some patients later require a repeat operation—redo-surgery, for example redo-valve replacement or redo-coronary artery bypass graft (CABG). Redo-surgery presents added challenges.  Adhesions or scars develop as a natural consequence of the body healing, and the heart is often encased by scars and attached intimately to surrounding vital structures. Repeat median sternotomy is the usual access to the heart. This procedure has to be done very carefully because the heart is just underneath the sternum. Opening the chest may take 30 minutes to an hour or more, depending on the severity of adhesions. Careful dissection is continued to free the heart before proceeding with the planned operation, which adds to the operative time.  Therefore, redo-operation is a much more involved operation, with higher risk of potential bleeding and complications.

Is it possible to do redo-cardiac surgery without blood transfusion? This report of a single-surgeon experience is important, since there are no large-series reports on this subject specifically involving Jehovah’s Witness patients, who for religious reasons absolutely do not accept blood transfusion.

Clinical Report

Forty-two (42) adult Jehovah’s Witness patients were reoperated. All the previous heart surgeries were by median sternotomy. There were twenty-eight (28) male and fifteen (15) female patients. The age range was thirty-three (33) to seventy-six (76) years. Thirty-one (31) of the cases were valve operations: twenty-three (23) single valve replacements and eight multiple valves. Of the multiple valves, five (5) were double valves—mitral valve replacements (MVR) and aortic valve replacements (AVR) and three were triple valves—MVR and AVR and tricuspid valve repairs (TVr). There were ten (10) redo-CABG. Six (6) patients had third-time operations. One of these had resection of the ascending aorta and Dacron graft repair for increasing size aneurysm, six cm in transverse diameter. This patient had the first aortic valve repair as a youngster because of a stenotic valve, followed years later with AVR. These operations are summarized in the following table:  

Redo-Cardiac Surgery

(n = 42)

Results:

All the redo-surgery patients survived their operations except one. The 30-day mortality rate is 2.3%. The patient who did not make it expired 22 days after surgery because of complication of CVA (cerebro-vascular accident) unrelated to blood loss or anemia. There was no significant bleeding encountered in the entire series.

About the Author

Manuel R. Estioko, MD is a Cardiac Surgeon from Los Angeles, California. He first developed an interest and involvement in Bloodless Surgery because of the very high incidence of Hepatitis C in open heart patients (18 % in New York City). At that time (late 1960’s & 1970):

• Almost all patients received blood transfusion, the early heart/lung machines required high volume prime with use of blood.
• Blood was obtained from donors with questionable health through commercial blood banking,  (the change to all volunteer donors came years later).
• There was no blood test for Hepatitis.

In 1996, Dr. Estioko coined and popularized the term “Transfusion Free Surgery” which is the other widely used designation for Bloodless Surgery.

Abstract

Perioperative blood loss is a significant concern for patients undergoing total joint arthroplasty. A growing body of evidence has shown tranexamic acid (TXA) to be effective in decreasing perioperative blood loss and transfusion requirements in both primary and revision hip and knee arthroplasty. Dr. Penn reports using TXA in successful hip replacement in a paitent with cardiac arrhythmia.

Report

A 53-year-old male Jehovah’s Witness presented with severe osteoarthritis of the left hip. He had long-term non-operative management including exercise, NSAIDs, and intra-articular injections. Ultimately, these didn’t provide lasting relief and he opted for hip replacement. Medical issues included cardiac arrhythmia, chronic back issues, hypertension and elevated cholesterol. His pre-operative Hgb was 16.7. In December 2015 he underwent a left total hip replacement through an anterior approach. Peri- operative management included normothermia, closed loop cell saver, and 1 gram tranexamic acid administered IV one hour pre-incision, with intraoperative administration as a direct application into the surgical wound right before closure. Intra-op blood loss was measured to be 500 ml, with 400 ml returned through the closed loop cell saver. Post-operatively his Hgb was 15.4 in the recovery room, dropping to 14.1, noted a week later when he was seen in the ER for opiate induced constipation. 2 weeks post-operatively, he was walking with a cane. At 2 months his issues were all back related, and the left hip was essentially pain free. He went on to have back surgery 5 months after his hip surgery. He was seen for routine x-ray follow-up at 1 and 2 years post-surgery and continues to do well. Next x-rays are scheduled for the 5-year point from his surgery.

Dr. Penn Notes:

The TXA comes as 1 gram in a 10 mL vial. The pre-operative dose is given within the hour before

incision, 1 gram IV over 10 minutes or more. Sometimes it is given full strength, but some of the nurses will dilute it with 10 mL of normal saline, doubling the volume. The reason it is given slowly is because it can cause nausea if given too fast. The exact timing of the pre-operative administration isn’t critical.

The topical is undiluted 1 gram placed into the wound at closure.

An additional gram around 3 hours post-OR was tried but seemed to cause a leukocytosis with some consistency. The third dose didn’t seem to make a difference with respect to the postoperative Hgb. No special consideration is given for presence of stents or anything else, as this material hasn’t been found to be thrombogenic. There is evidence that oral preoperative dosing is as effective as IV, but since our patients are NPO, we opt for the IV.

Abstract

Perioperative blood loss is a significant concern for patients undergoing total joint arthroplasty. A growing body of evidence has shown tranexamic acid (TXA) to be effective in decreasing perioperative blood loss and transfusion requirements in both primary and revision hip and knee arthroplasty. Dr. Penn reports using TXA in a successful total knee replacement without blood transfusion for a patient previously refused treatment at another hospital.

Case Report

A 65 year-old male Jehovah’s Witness presented with severe osteoarthritis in both knees, worse on the right. It was present for many years, but a motor vehicle accident had worsened his symptoms more recently. He had extensive non-operative treatment for several years. He was scheduled in a neighboring community for a total knee replacement, and his surgeon was aware that he is one of Jehovah’s Witnesses. At the last minute, his surgeon, because of the patient’s refusal of blood transfusion, canceled his surgery. He was seen and evaluated in our clinic and was felt to be a reasonable candidate for Total Knee Arthroplasty. His pre-op Hgb was 12.6 initially, but improved to 13.2, which was only mildly anemic, with oral iron therapy.1 Other issues were history of stroke, hypertension, and dyslipidemia. His surgery was in the spring of 2017. Closed loop cell saver and tranexamic acid were used – one gram administered IV one hour pre-operatively and one gram administered directly into the surgical wound right before closure. His blood loss at surgery was 200 ml, not enough for cell saver return. Post-op he did well and at two months was released from current care. He was doing well at one-year follow-up.

Dr. Penn Notes:

The TXA comes as 1 gram in a 10 mL vial. The pre-operative dose is given within the hour before incision, 1 gram IV over 10 minutes or more. Sometimes it is given full strength, but some of the nurses will dilute it with 10 mL of normal saline, doubling the volume. The reason it is given slowly is because it can cause nausea if given too fast. The exact timing of the pre-operative administration isn’t critical.

The topical is undiluted 1 gram placed into the wound at closure.

1 Recent studies have determined that twice-daily or daily dosing with oral iron triggers Hepcidin production in the gut, which in turn blocks iron absorption. The current recommended approach is a single dose every other day – http://www.hematology.org/Thehematologist/Diffusion/8265.aspx.

Abstract

Perioperative blood loss is a significant concern for patients undergoing total joint arthroplasty. A growing body of evidence has shown tranexamic acid (TXA) to be effective in decreasing perioperative blood loss and transfusion requirements in both primary and revision hip and knee arthroplasty. Dr. Penn reports using TXA in successful total knee replacement in an 83-year-old female with kidney disease.

Report

An 83 year-old female Jehovah’s Witness presented with severe osteoarthritis in her right knee. She had pain for several years, but in the spring of 2017 had significant worsening of symptoms making walking difficult. She had a history of well-

controlled hypertension & kidney disease, as well as a TIA in the past. Her only surgery was a C-section as a young woman. Initially she was treated with activity modification, OTC analgesics and a steroid injection, but she did not get significant lasting relief and so presented for a total knee replacement. Because of her kidney disease, she was chronically anemic with a pre-op Hgb of 10.6 – too high for erythropoietin. Discussed with her was the use of a tourniquet, and closed loop cell saver intra-operatively, use of tranexamic acid preoperatively as well as meticulous tissue handling. Her surgery took place in late summer 2017. One gram of tranexamic acid was administered by IV 1 hour pre-operatively and 1 gram as a direct application into the surgical site right before closure. Her blood loss was 200 ml – not enough for cell saver return. Post- operatively she went through her rehabilitation without difficulty. At 8 weeks, she was using a cane and having very little discomfort. She was released with the plan of seeing her in 1 year for x-ray follow-up.

Dr. Penn Notes:

The TXA comes as 1 gram in a 10 mL vial. The pre-operative dose is given within the hour before incision, 1 gram IV over 10 minutes or more. Sometimes it is given full strength, but some of the nurses will dilute it with 10 mL of normal saline, doubling the volume. The reason it is given slowly is because it can cause nausea if given too fast. The exact timing of the pre-operative administration isn’t critical.

The topical is undiluted 1 gram placed into the wound at closure.

An additional gram around 3 hours post-OR was tried but seemed to cause a leukocytosis with some consistency. The third dose didn’t seem to make a difference with respect to the postoperative Hgb. No special consideration is given for presence of stents or anything else, as this material hasn’t been found to be thrombogenic. There is evidence that oral preoperative dosing is as effective as IV, but since our patients are NPO, we opt for the IV.