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The effects of cardiopulmonary bypass on patients who have active or dormant malaria are unknown. What is known is that malaria-induced hemolysis can be exacerbated by cardiopulmonary bypass.
We report 3 cases in which patients with active or dormant malaria underwent open-heart surgery. Two of them received quinine prophylaxis, and the 3rd patient (who presented with an active infection) received longer-term preoperative treatment with quinine. In all 3 cases, the surgery was performed uneventfully.
We suggest preoperative quinine prophylaxis for patients with a history of malaria whose blood smears are negative for parasites, and we advocate more radical preoperative treatment with quinine for patients whose blood smears are positive at presentation. These measures appear to prevent hemolysis and fever during both the preoperative and postoperative periods. However, there is need of a multicenter study to ascertain the actual effects of cardiopulmonary bypass on patients with malaria.
Malaria results from the infection of the liver and erythrocytes by various members of the genus Plasmodium. Hemolysis is a common complication of malaria that can be exacerbated by cardiopulmonary bypass (CPB).1 Many patients who undergo open-heart surgery have at some time been infected by the malaria parasite, but the effects of CPB on these patients are not well known. A published report on the performance of CPB in a patient with an active case of malaria documented increased hemolysis without adverse outcome.1 We report 3 additional cases, in which we administered quinine as prophylaxis.
In June 2007, a 50-year-old man from Côte d'Ivoire was admitted for a coronary artery bypass. He was found to have a history of 3 episodes of malaria within the 4 years previous to admission. However, his blood smear was negative for parasites. As prophylaxis against excessive lysis of red blood cells while the patient was on CPB, we started him on intravenous quinine at 25 mg/kg a day. Treatment was kept up for 7 preoperative days, during which no side effect of the treatment was noted. At this time, we decided to proceed with surgery.
Preoperative laboratory results were within normal limits (Table I), with a hematocrit of 43.2 mL/dL and creatine level of 5 mg/L.
Surgery was performed using moderate hypothermic (32°C) CPB. A hollow-fiber membrane oxygenator and a roller pump were used. Myocardial preservation was achieved by the intermittent administration of cold crystalloid cardioplegic solution and the topical use of ice slush. During the intervention, the patient's hematocrit was around 31.0 to 32.0 mL/dL and no blood transfusion was required; no sign of excessive hemolysis was noted during bypass.
We performed triple coronary artery bypass grafting (CABG). The aortic cross-clamp time was 45 minutes, and total bypass time was 60 minutes. Surgical bleeding was 850 mL in total. The patient was weaned from CPB with pharmacologic support.
He was extubated within 6 hours. No excessive hemolysis nor neurologic symptoms occurred. The treatment with quinine was continued through the 7th postoperative day. The patient was satisfactorily ambulatory and was discharged from the hospital on the 10th postoperative day.
In November 2007, a 48-year-old woman, originally from Central Africa, was admitted for surgical repair of a thoracic aneurysm. She had a history of many episodes of malaria, recurrent from a single infection. Transesophageal echocardiography and thoracic angiotomography showed an aneurysm of the aortic arch that extended to the descending aorta. Preoperative coronary angiography did not reveal any lesion. Preoperative laboratory results (Table I) showed anemia with a hematocrit of 35.0 mL/dL. The blood smear was negative for parasites. Again, prophylaxis with intravenous quinine at 25 mg/kg a day was started and then continued for 7 days before proceeding with surgery.
Surgery was performed with CPB, using a hollow-fiber membrane oxygenator and a roller pump. Myocardial preservation was achieved through the intermittent administration of cold crystalloid cardioplegic solution and the topical use of ice slush. During 35 minutes of deep hypothermic arrest, we reconstructed the aortic arch via the elephant-trunk technique.
The patient needed 3 units of packed red blood cells during bypass in order to correct a hematocrit of 17.0 mL/dL, but no sign of excessive hemolysis was noted during bypass. The aortic cross-clamp time was 60 minutes, and the total bypass time was 90 minutes. Surgical bleeding was 1,250 mL in total. The patient was weaned from CPB with pharmacologic support.
She was extubated within 15 postoperative hours. No excessive hemolysis nor neurologic symptoms occurred postoperatively. As in the case of patient 1, the treatment with quinine was continued through the 7th postoperative day, and the patient was discharged from the hospital on the 15th postoperative day.
In July 2008, a 7-year-old girl—originally from Gabon, and recently diagnosed with severe mitral and tricuspid valvular insufficiency in association with Marfan syndrome—was scheduled for mitral valve replacement and tricuspid valve repair with an annuloplasty ring.
Five days before the scheduled date of surgery, the patient developed high fever with shaking chills. Malaria was suspected, and a blood smear positive for P. falciparum confirmed the diagnosis. A curative treatment with intravenous quinine at 25 mg/kg a day was started. Upon obtaining a negative blood smear on the 7th day of treatment, we continued the therapy for a 2nd preoperative week, at the end of which we proceeded with surgery. Postoperatively, we continued the intravenous quinine for another week (3 weeks of quinine therapy altogether). The patient remained free of fever throughout.
Preoperative laboratory results were within normal limits (Table I), with a hematocrit of 36.0 mL/dL and a creatine level of 6 mg/L.
Surgery was performed with the aid of normothermic (37°C) CPB. A hollow-fiber membrane oxygenator and a roller pump were used. Myocardial preservation was achieved by means of the intermittent administration of cold crystalloid cardioplegic solution and the topical use of ice slush. The patient received 2 units of packed red blood cells during bypass to correct a hematocrit of 19.0 mL/dL consequent to hemodilution. The pump run was uneventful, with no signs of excessive hemolysis during bypass. The urine remained clear during the procedure. The mitral valve was replaced with a 31-mm double-leaflet mechanical valve, and the tricuspid valve was spared through use of a 32-mm Carpentier-Edwards ring.
The aortic cross-clamp time was 70 minutes, and the total bypass time was 85 minutes. Surgical bleeding was 530 mL in total. The patient was weaned from CPB with pharmacologic support. Postoperative recovery was without incident, and the patient was weaned from the respirator and extubated within 18 hours. She was ambulatory on the 6th postoperative day and was discharged from the hospital on the 12th postoperative day.
Two patients had a history of treated malaria, with absence of symptoms and negative blood smears (Table I). We chose treatment with quinine for 15 days (including the day of operation), beginning 7 days before surgery and ending 7 days after surgery, in order to prevent relapse of the malaria.
In the 3rd patient, because of a positive blood smear, a more radical quinine therapy was decided upon. As recommended by the World Health Organization,2 we performed quinine therapy for 7 days and obtained a negative blood smear. We then continued the therapy for a 2nd preoperative week (at the end of which we operated) and for 1 additional week thereafter. After 3 weeks of quinine therapy, the risk of relapse is minor.
In the 3 patients, no increase in hemolysis was noted either during CPB or after the procedure (Table I). We did not note any instance of postoperative fever, and surgical bleeding was in the normal range.
Performing CPB on a patient with a history of malaria can increase hemolysis and perhaps induce a relapse of the malaria.1 There might be adverse outcomes that have not been documented, because knowledge about the effects of CPB on malaria patients is scant.
In our 3 patients, the aim of the treatment with quinine was to prevent perioperative and postoperative accidents that might accompany the parasite's arousal from dormancy.3 We used quinine because the 3 patients came from parts of the world where the resistance of malaria to antimalarial drugs—especially to chloroquine and mefloquine—is high. Furthermore, we considered malaria found in association with cardiac disease to be a severe form of malaria.2
Most cases of malaria that have been reported after open-heart surgery have been attributed to blood transfusion, but relapse of prior disease has also been implicated,4 and the possibility of relapse induction by major surgery or blood transfusion has been hypothesized1 because of the traumatic immunosuppressive action of these procedures. Cardiopulmonary bypass—which has even greater immunosuppressive effects—is easily suspect as a factor in the induction of malaria relapse.
Malaria, via blood transfusion, can also cause fever after open-heart surgery and has been implicated in 2.4% of such cases,5 but postoperative fever indicative of relapse is also seen in patients from malaria-endemic areas.6 Diagnosis of malaria can be difficult because of the many competing possibilities in differential diagnosis, so the cardiac surgery team should be aware of malaria as a possibility in both malaria-free and malaria-endemic areas; clearly, patients or blood donors who have moved from (or recently visited) an endemic area are potential victims or sources of the infection.
Finally, avoiding CPB, especially in patients who are to undergo CABG, might be a solution for a patient with a history of malaria7—provided that malaria is really a valid indication for off-pump CABG surgery.
Cardiopulmonary bypass appears to be safe, after short-term quinine therapy, in patients who have active malaria infections or histories of malaria. The aim is to prevent the parasite's arousal from dormancy and the consequent sequelae of excessive hemolysis and fever. However, on the basis of our 3 cases we do not know if the same preventive measures can be applied successfully to all situations. The heterogeneity of malaria complicates the matter further. A multicenter study should be performed to evaluate the effects of pre-existing malaria on patients who undergo CPB.
Address for reprints: El Mehdi Moutaouekkil, MD, BP 6312, Madinat Al Irfane, Rabat, Morocco