Charles M. Haberkern

A Comparison of Conservative and Aggressive Transfusion Regimens in the Perioperative Management of Sickle Cell Disease

BACKGROUND Preoperative transfusions are frequently given to prevent perioperative morbidity in patients with sickle cell anemia. There is no consensus, however, on the best regimen of transfusions for this purpose. METHODS We conducted a multicenter study to compare the rates of perioperative complications among patients randomly assigned to receive either an aggressive transfusion regimen designed to decrease the hemoglobin S level to less than 30 percent (group 1) or a conservative regimen designed to increase the hemoglobin level to 10 g per deciliter (group 2). RESULTS Patients undergoing a total of 604 operations were randomly assigned to group 1 or group 2. The severity of the disease, compliance with the protocol, and the types of operations were similar in the two groups. The preoperative hemoglobin level was 11 g per deciliter in group 1 and 10.6 g per deciliter in group 2. The preoperative value for hemoglobin S was 31 percent in group 1 and 59 percent in group 2. The most frequent operations were cholecystectomies (232), head and neck surgery (156), and orthopedic surgery (72). With the exception of transfusion-related complications, which occurred in 14 percent of the operations in group 1 and in 7 percent of those in group 2, the frequency of serious complications was similar in the two groups (31 percent in group 1 and 35 percent in group 2). The acute chest syndrome developed in 10 percent of both groups and resulted in two deaths in group 1. A history of pulmonary disease and a higher risk associated with surgery were significant predictors of the acute chest syndrome. CONCLUSIONS A conservative transfusion regimen was as effective as an aggressive regimen in preventing perioperative complications in patients with sickle cell anemia, and the conservative approach resulted in only half as many transfusion-associated complications.

Anesthesia-related cardiac arrest in children: initial findings of the Pediatric Perioperative Cardiac Arrest (POCA) Registry.

Background The Pediatric Perioperative Cardiac Arrest (POCA) Registry was formed in 1994 in an attempt to determine the clinical factors and outcomes associated with cardiac arrest in anesthetized children. Methods Institutions that provide anesthesia for children are voluntarily enrolled in the POCA Registry. A representative from each institution provides annual institutional demographic information and submits anonymously a standardized data form for each cardiac arrest (defined as the need for chest compressions or as death) in anesthetized children 18 yr of age or younger. Causes and factors associated with cardiac arrest are analyzed. Results In the first 4 yr of the POCA Registry, 63 institutions enrolled and submitted 289 cases of cardiac arrest. Of these, 150 arrests were judged to be related to anesthesia. Cardiac arrest related to anesthesia had an incidence of 1.4 ± 0.45 (mean ± SD) per 10,000 instances of anesthesia and a mortality rate of 26%. Medication-related (37%) and cardiovascular (32%) causes of cardiac arrest were most common, together accounting for 69% of all arrests. Cardiovascular depression from halothane, alone or in combination with other drugs, was responsible for two thirds of all medication-related arrests. Thirty-three percent of the patients were American Society of Anesthesiologists physical status 1–2; in this group, 64% of arrests were medication-related, compared with 23% in American Society of Anesthesiologists physical status 3–5 patients (P < 0.01). Infants younger than 1 yr of age accounted for 55% of all anesthesia-related arrests. Multivariate analysis demonstrated two predictors of mortality: American Society of Anesthesiologists physical status 3–5 (odds ratio, 12.99; 95% confidence interval, 2.9–57.7), and emergency status (odds ratio, 3.88; 95% confidence interval, 1.6–9.6). Conclusions Anesthesia-related cardiac arrest occurred most often in patients younger than 1 yr of age and in patients with severe underlying disease. Patients in the latter group, as well as patients having emergency surgery, were most likely to have a fatal outcome. The identification of medication-related problems as the most frequent cause of anesthesia-related cardiac arrest has important implications for preventive strategies.

Anesthesia-Related Cardiac Arrest in Children: Update from the Pediatric Perioperative Cardiac Arrest Registry

BACKGROUND:The initial findings from the Pediatric Perioperative Cardiac Arrest (POCA) Registry (1994–1997) revealed that medication-related causes, often cardiovascular depression from halothane, were the most common. Changes in pediatric anesthesia practice may have altered the causes of cardiac arrest in anesthetized children. METHODS:Nearly 80 North American institutions that provide anesthesia for children voluntarily enrolled in the Pediatric Perioperative Cardiac Arrest Registry. A standardized data form for each perioperative cardiac arrest in children ≤18 yr of age was submitted anonymously. We analyzed causes of anesthesia-related cardiac arrests and related factors in 1998–2004. RESULTS:From 1998 to 2004, 193 arrests (49%) were related to anesthesia. Medication-related arrests accounted for 18% of all arrests, compared with 37% from 1994 to 1997 (P < 0.05). Cardiovascular causes of cardiac arrest were the most common (41% of all arrests), with hypovolemia from blood loss and hyperkalemia from transfusion of stored blood the most common identifiable cardiovascular causes. Among respiratory causes of arrest (27%), airway obstruction from laryngospasm was the most common cause. Vascular injury incurred during placement of central venous catheters was the most common equipment-related cause of arrest. The cause of arrest varied by phase of anesthesia care (P < 0.01). Cardiovascular and respiratory causes occurred most commonly in the surgical and postsurgical phases, respectively. CONCLUSIONS:A reduction in the proportion of arrests related to cardiovascular depression due to halothane may be related to the declining use of halothane in pediatric anesthetic practice. The incidence of the most common remaining causes of arrest in each category may be reduced through preventive measures.

Induction, recovery, and safety characteristics of sevoflurane in children undergoing ambulatory surgery. A comparison with halothane.

Background Sevoflurane is an inhalational anesthetic with characteristics suited for use in children. To determine whether the induction, recovery, and safety characteristics of sevoflurane differ from those of halothane, the following open‐labeled, multicenter, randomized, controlled, phase III study in children undergoing ambulatory surgery was designed. Methods Three hundred seventy‐five children, ASA physical status 1 or 2, were randomly assigned in a 2:1 ratio to receive either sevoflurane or halothane, both in 60% N2 O and 40% O2. Anesthesia was induced using a mask with an Ayres t piece or Bain circuit in four of the centers and a mask with a circle circuit in the fifth center. Maximum inspired concentrations during induction of anesthesia were 7% sevoflurane and 4.3% halothane. Anesthesia was maintained by spontaneous ventilation, without tracheal intubation. End‐tidal concentrations of both inhalational anesthetics were adjusted to 1.0 MAC for at least 10 min before the end of surgery. Induction and recovery characteristics and all side effects were recorded. The plasma concentration of inorganic fluoride was measured at induction of and 1 h after anesthesia. Results During induction of anesthesia, the time to loss of the eyelash reflex with sevoflurane was 0.3 min faster than with halothane (P < 0.001). The incidence of airway reflex responses was similar, albeit infrequent with both anesthetics. The total MAC *symbol* h exposure to sevoflurane was 11% less than the exposure to halothane (P < 0.013), although the end‐tidal MAC multiple during the final 10 min of anesthesia was similar for both groups. Early recovery as evidenced by the time to response to commands after sevoflurane was 33% more rapid than it was after halothane (P < 0.001), although the time to discharge from hospital was similar for both anesthetics. The mean (+/‐SD) plasma concentration of inorganic fluoride 1 h after discontinuation of sevoflurane was 10.3+/‐3.5 micro Meter. The overall incidence of adverse events attributable to sevoflurane was similar to that of halothane, although the incidence of agitation attributable to sevoflurane was almost threefold greater than that attributable to halothane (P < 0.004). Conclusions Sevoflurane compared favorably with halothane. Early recovery after sevoflurane was predictably more rapid than after halothane, although this was not reflected in a more rapid discharge from the hospital. The incidence of adverse events was similar for both anesthetics. Clinically, the induction, recovery, and safety characteristics of sevoflurane and halothane are similar. Sevoflurane is a suitable alternative to halothane for use in children undergoing minor ambulatory surgery.

Anesthesia-Related Cardiac Arrest in Children with Heart Disease: Data from the Pediatric Perioperative Cardiac Arrest (POCA) Registry

BACKGROUND: From 1994 to 2005, the Pediatric Perioperative Cardiac Arrest Registry collected data on 373 anesthesia-related cardiac arrests (CAs) in children, 34% of whom had congenital or acquired heart disease (HD). METHODS: Nearly 80 North American institutions that provide anesthesia for children voluntarily enrolled in the Pediatric Perioperative Cardiac Arrest Registry. A standardized data form for each perioperative CA in children 18 years old or younger was submitted anonymously. We analyzed causes of and outcomes from anesthesia-related CA in children with and without HD. RESULTS: Compared with the 245 children without HD, the 127 children with HD who arrested were sicker (92% vs 62% ASA physical status III–V; P < 0.01) and more likely to arrest from cardiovascular causes (50% vs 38%; P = 0.03), although often the exact cardiovascular cause of arrest could not be determined. Mortality was higher in patients with HD (33%) than those without HD (23%, P = 0.048) but did not differ when adjusted for ASA physical status classification. More than half (54%) of the CA in patients with HD were reported from the general operating room compared with 26% from the cardiac operating room and 17% from the catheterization laboratory. The most common category of HD lesion in patients suffering CA was single ventricle (n = 24). At the time of CA, most patients with congenital HD were either unrepaired (59%) or palliated (26%). Arrests in patients with aortic stenosis and cardiomyopathy were associated with the highest mortality rates (62% and 50%, respectively), although statistical comparison was precluded by small sample size for some HD lesions. CONCLUSIONS: Children with HD were sicker compared with those without HD at the time of anesthesia-related CA and had a higher mortality after arrest. These arrests were reported most frequently from the general operating room and were likely to be from cardiovascular causes. The identification of causes of and factors relating to anesthesia-related CA suggests possible strategies for prevention.

The perioperative complication rate of orthopedic surgery in sickle cell disease: Report of the national sickle cell surgery study group

Orthopedic disease affects the majority of sickle cell anemia patients of which aseptic necrosis of the hip is the most common, occurring in up to 50% of patients. We conducted a multicentered study to determine the perioperative complications among sickle cell patients assigned to different transfusion regimens prior to orthopedic procedures: 118 patients underwent 138 surgeries. The overall serious complication rate was 67%. The most common of these were excessive intraoperative blood loss, defined as in excess of 10% of blood volume. The next most common complication was sickle cell‐related events (acute chest syndrome or vaso‐occlusive crisis), which occurred in 17% of cases. While preoperative transfusion group assignment did not predict overall complication rates, higher risk procedures were associated with significantly higher rates of overall complications. Transfusion complications were experienced by 12% of the patients. Two patients died following surgery. Both deaths were associated with an acute pulmonary event. The 52 patients undergoing hip replacements experienced the highest rate of complications with excessive intraoperative blood loss occurring in the majority of patients. Sickle cell‐related events occurred in 19% of patients, and surgical complications occurred after 15% of hip replacements and included postoperative hemorrhage, dislocated prosthesis, wound abscess, and rupture of the femoral prosthesis. There were twenty‐two hip coring procedures. Acute chest syndrome occurred in 14% of the patients. Overall, decompression coring was a safer, shorter operation. A randomized prospective trial to determine the perioperative and long‐term efficacy of core decompression for avascular necrosis of the hip in sickle cell disease is needed. In conclusion, this study demonstrates a high rate of perioperative complications despite compliance with sickle cell perioperative care guidelines. Pulmonary complications and transfusion reactions were common. This study supports the results previously published by the National Preoperative Transfusion in Sickle Cell Disease Group. These results stated that a conservative preoperative transfusion regimen to bring hemoglobin concentration to between 9 and 11 g/dl was as effective as an aggressive transfusion regimen in which the hemoglobin S level was lowered to 30%. Am. J. Hematol. 62:129–138, 1999.

Acute Appendicitis Risks of Complications: Age and Medicaid Insurance

Objectives. To describe the epidemiology of acute appendicitis in children from Washington State, and to determine important risk factors for complications. Design. Retrospective cohort study. Setting. All children (<17 years old) treated in Washington State who were identified by hospital discharge diagnosis codes from 1987 through 1996. Methods. The hospital discharge data were reviewed for all children with a primary diagnosis code for acute appendicitis. Complicated disease was defined as perforation or abscess formation. Results. Young children (0–4 years old) had the lowest annual incidence of acute appendicitis, but they had a 5-fold increased risk of complicated disease (odds ratio: 4.9; 95% confidence interval: 4.0–5.9), compared with teenagers. Children with Medicaid insurance had a 1.3-fold increased risk of complicated disease, compared with children with commercial insurance (odds ratio: 1.3: 95% confidence interval: 1.2–1.4). Children with Medicaid insurance had significantly longer average length of stay (4.0 ± 3.7 days) than all other payers (commercial insurance: 3.3 ± 4.0 days; health maintenance organization: 3.5 ± 3.1 days; and self-insured: 3.7 ± 5.8 days). Conclusions. Very young children had the greatest risk of complicated disease. Children with Medicaid insurance had increased risk of complicated disease, compared with children with commercial health insurance and longer length of stay. Additional studies are needed to evaluate barriers to care for children with Medicaid insurance.

Physical therapy alone compared with core decompression and physical therapy for femoral head osteonecrosis in sickle cell disease: Results of a multicenter study at a mean of three years after treatment

BACKGROUND Osteonecrosis of the femoral head is a common complication in patients with sickle cell disease, and collapse of the femoral head occurs in 90% of patients within five years after the diagnosis of the osteonecrosis. However, the efficacy of hip core decompression to prevent the progression of osteonecrosis in these patients is still controversial. METHODS In a prospective multicenter study, we evaluated the safety of hip core decompression and compared the results of decompression and physical therapy with those of physical therapy alone for the treatment of osteonecrosis of the femoral head in patients with sickle cell disease. Forty-six patients (forty-six hips) with sickle cell disease and Steinberg Stage-I, II, or III osteonecrosis of the femoral head were randomized to one of two treatment arms: (1) hip core decompression followed by a physical therapy program or (2) a physical therapy program alone. Eight patients withdrew from the study, leaving thirty-eight who participated. RESULTS Seventeen patients (seventeen hips) underwent decompression combined with physical therapy, and no intraoperative or immediate postoperative complications occurred. Twenty-one patients (twenty-one hips) were treated with physical therapy alone. After a mean of three years, the hip survival rate was 82% in the group treated with decompression and physical therapy and 86% in the group treated with physical therapy alone. According to a modification of the Harris hip score, the mean clinical improvement was 18.1 points for the patients treated with hip core decompression and physical therapy compared with 15.7 points for those treated with physical therapy alone. With the numbers studied, the differences were not significant. CONCLUSIONS In this randomized prospective study, physical therapy alone appeared to be as effective as hip core decompression followed by physical therapy in improving hip function and postponing the need for additional surgical intervention at a mean of three years after treatment.

Single-Dose Ondansetron Prevents Postoperative Vomiting in Pediatric Outpatients

This randomized, double-blind, parallel-group, multicenter study evaluated the safety and efficacy of ondansetron (0.1 mg/kg to 4 mg intravenously) compared with placebo in the prevention of postoperative vomiting in 429 ASA status I-III children 1-12 yr old undergoing outpatient surgery under nitrous oxide- and halothane-based general anesthesia. The results show that during both the 2-h and the 24-h evaluation periods after discontinuation of nitrous oxide, a significantly greater percentage of ondansetron-treated patients (2 h 89%, 24 h 68%) compared with placebo-treated patients (2 h 71%, 24 h 40%) experienced complete response (i.e., no emetic episodes, not rescued, and not withdrawn; P < 0.001 at both time points). Ondansetron-treated patients reached criteria for home readiness one-half hour sooner than placebo-treated patients (P < 0.05). The age of the child, use of intraoperative opioids, type of surgery, and requirement to tolerate fluids before discharge may also have affected the incidence of postoperative emesis during the 0- to 24-h observation period. Use of postoperative opioids did not have any effect on complete response rates in this patient population. We conclude that the prophylactic use of ondansetron reduces postoperative emesis in pediatric patients, regardless of the operant influential factors. Implications: Postoperative nausea and vomiting often occur after surgery and general anesthesia in children and are the major reason for unexpected hospital admission after ambulatory surgery. Our study demonstrates that the prophylactic use of a small dose of ondansetron reduces postoperative vomiting in pediatric patients. (Anesth Analg 1997;85:538-45)

Morphine pharmacokinetics during continuous infusion of morphine sulfate for infants receiving extracorporeal membrane oxygenation.

OBJECTIVES To determine a) if serum morphine concentration changes during the first 3 hrs of extracorporeal membrane oxygenation (ECMO); and b) if absorption of morphine onto the membrane oxygenator is responsible for these changes. Also, morphine clearance during the first 5 days of ECMO was studied. DESIGN Prospective, open-label study with consecutive patient enrollment. SETTING Neonatal intensive care unit at a university-affiliated, childrens hospital. SUBJECTS Eleven neonates with severe persistent pulmonary hypertension of the newborn receiving continuous intravenous infusions of morphine sulfate and requiring ECMO. INTERVENTIONS Blood samples were obtained from the subjects and ECMO circuits at predetermined time intervals. MEASUREMENTS AND MAIN RESULTS Serum morphine concentration was determined using high-performance liquid chromatography. Morphine concentrations were no different from baseline at 5 mins, 1 hr, or 3 hrs after beginning ECMO. There was no significant difference in morphine concentration from samples taken immediately proximal and distal to the membrane oxygenator at 5 mins, 1 hr, and 3 hrs after the start of ECMO. Morphine clearance was calculated on days 1, 3, and 5 of ECMO. The mean value for morphine clearance was 11.7 +/- 9.3 (SD) ml/min/kg (range 2.6 to 34.5). CONCLUSIONS The initiation of ECMO does not lead to a significant decrease in serum morphine concentration and there is no uptake of morphine onto the membrane oxygenator of the ECMO circuit. Morphine clearance for infants receiving ECMO is variable.