Ultrasound-Guided Regional Anesthesia in a Glucose-6-Phosphate Dehydrogenase (G6PD)-Deficient Geriatric Trauma Patient

Abstract

Objective: Glucose-6-phosphate dehydrogenase (G6PD) deficiency is a genetic enzymatic disorder causing hemolytic anemia. Exposure to drugs is considered to be the most common cause of acute hemolysis in patients with G6PD deficiency. Experience with regional anesthesia, in particular peripheral nerve blocks, is rarely described in patients with G6PD deficiency, but is of great clinical interest. For this reason, we now report on the successful management of ultrasound-guided axillary brachial plexus block in a patient with geriatric G6PD deficiency. Case report: A female, 75-year-old geriatric trauma patient with G6PD deficiency and a fracture of the left forearm, was scheduled for osteosynthesis of the left forearm. For surgery regional anesthesia with ultrasound-guided axillary brachial plexus block with 30 mL bupivacaine 0.5% was established. Surgical operation und postoperative course were uneventful and with no signs of hemolysis. Conclusion: Ultrasound-guided axillary brachial plexus block with bupivacaine was a safe and effective technique in this patient with G6PD deficiency. Peripheral nerve block is a major analgesic approach and of great value for anesthesiologists and surgeons, especially in our aging and multimorbid society.

Introduction

Glucose-6-phosphate dehydrogenase (G6PD) deficiency is an enzymopathy affecting human red blood cells. ¹ It is an X-linked, hereditary genetic defect prevalent in more than 400 million people worldwide. ¹ The G6PD is an enzyme necessary for the production of antioxidants that protect red blood cells from oxidative stressors. ¹ In the case of G6PD deficiency, red blood cells can be damaged by oxidative stresses caused by certain drugs, metabolic conditions, infections, ingestion of fava beans, ¹ or surgical interventions. ² Affected red blood cells are unable to scavenge the free radicals, resulting in hemolysis. ³ Common clinical manifestations are acute hemolytic anemia, neonatal jaundice, or chronic nonspherocytic anemia. ⁴ Acute hemolysis due to exposure to oxidative agents is considered the most common adverse clinical consequence of G6PD deficiency ⁵ and poses a challenge for perioperative comanagement by anesthesiologists and surgeons. Peripheral nerve block is a popular and safe anesthesiological technique in geriatric patients in comparison to general anesthesia, because it has very few cardiovascular or pulmonary side effects. ⁶ The literature contains only rare case reports on regional anesthesia in patients with G6PD deficiency. Our experience with an ultrasound-guided peripheral nerve block in such a patient is thus of broad interest.

Here, we report on a patient with geriatric G6PD deficiency undergoing osteosynthesis under ultrasound-guided axillary brachial plexus block for a forearm fracture.

Case Report

A 75-year-old female with G6PD deficiency was admitted to our hospital following a skiing accident. A fracture of the distal radius was diagnosed. The geriatric trauma patient reported that she was diagnosed with G6PD deficiency some years ago. Cold-induced urticaria was known as a further comorbidity. The orthopedic surgeon indicated surgical management (open reduction and plating of the radius) of the fractured left arm. Our patient’s preference was given consideration in deciding for regional anesthesia over general anesthesia. Due to the advanced age of our patient (age 75) peripheral nerve block is definitely an appropriate anesthesiological method and entails very few cardiovascular or pulmonary side effects. ⁶ Our patient was fully orientated and cooperative, which is essential for the axillary brachial plexus block procedure. Preoperative blood coagulation, liver, and renal function values were in the normal range (activated partial thromboplastin time 28 seconds; prothrombin time 100%; thrombocytes 329 G/L; glutamic-oxalacetic transaminase (GOT) 24 U/L; glutamic/glutamate pyruvic transaminase (GPT) 9 U/L; gamma-GT 12 U/L; creatinine 0.88 mg/dL; glomerular filtraration rate >60 mL/min/1.73m²; potassium 4.5 mmol/L). Preoperative hemoglobin was 12.4 g/L.

In the operating room an ultrasound-guided axillary brachial plexus block was established with 30 mL of bupivacaine 0.5% (Actavis Group PTC ehf., Hafnarfjördur, Iceland). Since lidocaine can cause acute hemolysis in patients with G6PD deficiency, ^3,7 we used bupivacaine for axillary brachial plexus block in this case, which provided adequate analgesia. No additional intraoperative sedation or analgesia was necessary. The operation was completed after about 2 hours without any complications, and the patient was transferred to the recovery room without pain or any other complaints. Postoperative analgesia was maintained with 1g paracetamol intravenously (iv) and 3 mg piritramide iv. No hemolysis was noted during the perioperative period, hemoglobin 11.5 (12.4-10.4) g/L, free hemoglobin 23.4 mg/dL, bilirubin 0.41 (0.61-0.32) mg/dL, haptoglobin 235 (240-231) mg/dL, lactate dehydrogenase 212 (231-194) U/L, GPT 8 (9-5) U/L, GOT 21 (24-20) U/L, and potassium 4.4 (4.5-4.3) mmol/L. Additional hemolysis parameters such as reticulocytes, Coombs test, and peripheral blood smear were not evaluated, because there were no primary signs of hemolysis. The patient had a prolonged hospital stay of 6 days because of a local reaction without any sign of infection and not related to the G6PD deficiency.

Discussion

Most persons with G6PD deficiency are not aware of their enzyme defect. ⁴ They are asymptomatic until the disease manifests as acute hemolysis, usually after exposure to oxidative stress triggered by certain agents, infections, metabolic conditions, ingestion of fava beans, ⁴ or surgical interventions. ² Five classes of G6PD deficiency are distinguished according to the magnitude of the enzyme deficiency, with the subsequent risk of hemolysis ranging from severe enzyme defects with chronic hemolytic anemia (class I) to normal to slightly increased activity without clinical significance (class V). ^1,4 Careful preoperative medical history and the perioperative prevention of infections, ¹ hypothermia, ³ and certain metabolic conditions (diabetic ketoacidosis, hyperglycemia) are important to avoid hemolysis in patients with G6PD deficiency. ¹

The patient’s medical history noted a known G6PD deficiency over years without reported acute exacerbations, but gave no further information about the severity of the disease. Our patient is an active septogenarian, and it is thus unlikely that she is homozygous for enzymatic derangement. Since she also showed no overt signs of chronic hemolytic anemia, we expected a typically mild form of G6PD deficiency, probably class III. Furthermore, drugs used in the perioperative period were discussed with regard to their triggering hemolysis in G6PD-deficient patients (Table 1). However, there is no evidence-based global consensus on the use of local anesthetics or other medication in patients with G6PD deficiency. ⁵ Therefore, for safety reasons we chose an anesthesiological method that employs as few drugs as possible, while ensuring highest efficacy and safety.

Table 1.

List of Some Anesthesia and Perioperatively Relevant Drugs Used in Patients With G6PD-Deficient That (1) Can Be Administered Safely, (2) Should Be Avoided, and (3) Are Controversially Discussed in the Literature^a. ^{1 , 3 , 5 , 7 , 8 , 9 , 10}

Substance	Classified in references as
	Safe	Unsafe
Drugs that can be safely administered
Ketamine	1,8
Fentanyl	1,3,7,9,10
Propofol	1,3,9
Sodium thiopental	7
Succinylcholine	7
Bupivacaine	9
Drugs that should be avoided
Sevoflurane		1,3,8
Metoclopramide		7
Penicillin		7
Sulfonamide		7
Lidocaine		3
Toluidine blue		3,5,7
Drugs that are controversially discussed
Diazepam (valium)	1	3,8
Midazolam (dormicum)	1,3,9,10	8
Acetylsalicylic acid (aspirin)	5	5
Acetaminophen (paracetamol, tylenol)	5	3, 5
Metamizole sodium	5	5
Co-trimoxazole	5	5
Ciprofloxacin	5	5
Prilocaine	3	1
Isoflorane	7,10	1,3,8

^a No data could be found for remifentanil.

Ultrasound-guided regional anesthesia is a technique that entails fewer adverse effects and an excellent success rate accompanied by patient satisfaction and comfort. ^11,12 Direct visualization of anatomical structures and spread of local anesthetic are the main advantages of ultrasound-guided nerve blocks and result in highest efficacy, improved block quality, reduction of local anesthetic volume, and prevention of maldistribution. ¹² When compared to infra- and supraclavicular brachial plexus blocks, the axillary brachial plexus block is considered the safer approach for this type of surgery, because it involves a reduced risk of lesion of the phrenic nerve or the pneumothorax ¹³ . Especially in geriatric patients, who present with pulmonary diseases like emphysema, the axillary brachial plexus block is an option for forearm and hand surgery. Because of prolonged drug action in elderly persons, the duration of nerve block may be extended. ¹⁴ Additionally, if general anesthesia was necessary for surgery, total intravenous anesthesia with propofol ^1,3,9 and fentanyl ^1,3,7,9,10 would be presumed safe in patients with G6PD deficiency and would therefore also be an option. However, in elderly patients general anesthesia has some disadvantages when compared to regional anesthesia. In elderly patients undergoing general anesthesia pulmonary disorder, hypothermia, myocardial ischemia, and a longer recovery time are the most common problems encountered during the postoperative period. ¹⁴ Furthermore, in a narcotized patient it is not possible to intraoperatively identify immediate clinical signs of hemolysis like fatigue, back pain, headache, and dyspnea. Further signs of hemolysis such as hypotension, tachycardia, cyanosis, renal failure, dark urine, und disseminated intravascular coagulation ^{1 –4} may be attributed to other causes. ¹ Thus, based on the literature and our patient’s request we considered the use of bupivacaine in ultrasound-guided axillary brachial plexus block to be the safest and most effective means of anesthesia for our patient.

When using this anesthesiological management, we did not detect any signs of hemolysis in the perioperative period. Therefore, no additional therapy was necessary. Acute hemolysis occurs up to 3 days after exposure to triggering factors. ⁷ Typical laboratory workup reveals decreased hemoglobin and haptoglobin, whereas the levels of lactate dehydrogenase, unconjugated bilirubin, and reticulocytes are elevated. ^1,4 The Direct Coombs test should be negative, because G6PD deficiency is not an immune process. ¹ Peripheral blood smear can show Heinz bodies, schistocytes, and reticulocytes. ¹ Most cases of acute hemolysis do not require specific treatment. Treatment consists of eliminating the triggering factor and controlling the clinical symptoms.

From the orthopedic surgeon’s point of view the main advantage of a peripheral nerve block is the reduction in postoperative pain medication. ¹⁵ For the elderly patients this is an urgent need, as their high rate of relevant comorbidities limits pain treatment options in comparison to the younger population. ¹⁶ Furthermore, side effects of pain medication are more common in the elderly individuals and include gastrointestinal bleeding, cognitive deficits, and constipation. ¹⁷ For these reasons the peripheral nerve block is of great value for anesthesiologists and surgeons and has emerged as an important analgesic approach.

In conclusion, for regional anesthesia in patients with G6PD deficiency there is no evidence-based consensus on medication and G6PH deficiency. ⁵ Exposure to drugs can cause acute hemolysis and therefore a life-threatening situation in these patients. ⁵ We here demonstrate successful and safe perioperative comanagement by anesthesiologists and surgeons in a patient with geriatric G6PD deficiency achieved with an ultrasound-guided axillary brachial plexus block with bupivacaine.