Effects of age on the serum concentration of alpha 1-acid glycoprotein and the binding of lidocaine in pediatric patients.

We determined the effect of age on the serum concentration of alpha 1-acid glycoprotein (alpha 1-AGP) in venous blood from 134 subjects who ranged in age from preterm neonates to 18-year-old adolescents. The mean (+/- SD) serum concentration of alpha 1-AGP, determined by radial immunodiffusion, increased significantly with age: the concentration found in neonates was less than that found in infants which, in turn, was less than that found in older children (p less than 0.001). In addition, we determined the effect of alpha 1-AGP on the free fraction of lidocaine in four groups of infants and children who received intravenous lidocaine (1.5 mg/kg). The percentage of free lidocaine correlated inversely and linearly with the serum alpha 1-AGP concentration (r2 = 0.617; p less than 0.001). The percentage of free lidocaine in the five neonates exceeded that in the older age groups. We conclude that the serum concentration of alpha 1-AGP increases while the free fraction of lidocaine decreases from early infancy to adolescence.

Coagulation and fibrinolytic profile of paediatric patients undergoing cardiopulmonary bypass.

The haemostatic system and the use of heparin during cardiopulmonary bypass (CPB) have been studied extensively in adults but not in children. Results from adult trials cannot be extrapolated to children because of age-dependent physiologic differences in haemostasis. We studied 22 consecutive paediatric patients who underwent CPB at The Hospital for Sick Children, Toronto. Fibrinogen, factors II, V, VII, VIII, IX, XII, prekallikrein, protein C, protein S, antithrombin (AT), heparin cofactor II, alpha 2-macroglobulin, plasminogen, alpha 2-antiplasmin, tissue plasminogen activator (tPA), plasminogen activator inhibitor, thrombin-AT complexes (TAT), D-dimer, heparin (by both anti-factor Xa assay and protamine titration) and activated clotting time (ACT) were assayed perioperatively. The timing of the sampling was: pre heparin, post heparin, after initiation of CPB, during hypothermia, post hypothermia, post protamine reversal and 24 h post CPB. Plasma concentrations of all haemostatic proteins decreased by an average of 56% immediately following the initiation of CPB due to haemodilution. During CPB, the majority of procoagulants, inhibitors and some components of the fibrinolytic system (plasminogen, alpha 2 AP) remained stable. However, plasma concentrations of TAT and D-dimers increased during CPB showing that significant activation of the coagulation and fibrinolytic systems occurred. Mechanisms responsible for the activation of haemostasis are likely complex. However, low plasma concentrations of heparin (< 2.0 units/ml in 45% of patients) during CPB were likely a major contributing etiology. ACT values showed a poor correlation (r = 0.38) with heparin concentrations likely due to concurrent haemodilution of haemostatic factors, activation of haemostatic system, hypothermia and activation of platelets. In conclusion, CPB in paediatric patients causes global decreases of components of the coagulation and fibrinolytic systems, primarily by haemodilution and secondarily by consumption.

Influence of operations with cardiopulmonary bypass on polymorphonuclear leukocyte function in infants.

To determine the effect of operations with cardiopulmonary bypass on the immunologic function of polymorphonuclear leukocytes in infants, we studied polymorphonuclear leukocyte function and immunologic profile in 16 infants undergoing repair of congenital heart lesions. An oxygen/air/high-dose fentanyl anesthetic was used for all patients. Absolute neutrophil count increased significantly (p less than 0.05) after bypass and remained increased 48 hours afterward. Chemotaxis, random migration of polymorphonuclear leukocytes, and phagocytic index were unaffected, but bactericidal capacity decreased significantly immediately after cardiopulmonary bypass and remained decreased 48 hours later. Serum opsonizing capacity to bacterial and fungal antigens was variably altered, and complement factors 3 and 4 decreased significantly after cardiopulmonary bypass. Total hemolytic complement decreased significantly immediately after cardiopulmonary bypass and returned to normal by 48 hours. These data suggest that operations with cardiopulmonary bypass in infants significantly affect the immunologic function of polymorphonuclear leukocytes and result in consumption of complement.

The limits of detectable cerebral perfusion by transcranial Doppler sonography in neonates undergoing deep hypothermic low-flow cardiopulmonary bypass.

OBJECTIVE: Neurologic morbidity including seizures, abnormal neurologic function, and delayed psychomotor development continue to be significant problems for some patients undergoing operations for congenital heart disease, particularly for those subjected to deep hypothermic circulatory arrest. The technique of low-flow cardiopulmonary bypass has been advocated to decrease the incidence of neurologic sequelae. Our study examined the limits of detectable blood flow in the middle cerebral artery during low-flow cardiopulmonary bypass in 28 neonates undergoing the arterial switch procedure. METHODS: Cerebral blood flow velocity was measured noninvasively in the M1 segment of the middle cerebral artery with a 2 MHz range-gated pulsed-wave transcranial Doppler sonographic probe that was placed over the left temporal window. As part of the initiation of a planned period of deep hypothermic circulatory arrest, the cardiopulmonary bypass flow rate was decreased in stages to five low-flow rates (50, 40, 30, 20, and 10 ml/kg per minute). After a period of stabilization, cerebral blood flow velocities were recorded at each of the five low-flow rates and reported as a percentage of baseline. RESULTS: All 28 neonates had detectable perfusion in the middle cerebral artery at flow rates of 30 ml/kg per minute or higher. At flows of 20 and 10 ml/kg per minute, one and eight, respectively, of the 28 neonates had no detectable perfusion in the middle cerebral artery. CONCLUSIONS: Our data show that cerebral perfusion can be detected by transcranial Doppler sonography in the middle cerebral artery in some neonates at bypass pump flows as low as 10 ml/kg per minute. However, when transcranial Doppler sonography was used in our patient population, a minimum bypass flow rate of 30 ml/kg per minute was needed to detect cerebral perfusion in all neonates.

Myocardial performance after repair of congenital cardiac defects in infants and children. Response to volume loading.

The hemodynamic response to increasing left atrial pressure by volume loading was evaluated in 70 children during the first 24 hours after repair of congenital cardiac defects. The children were grouped into four diagnostic categories: atrial septal defect or pulmonary valve stenosis (n = 8), ventricular septal defect (n = 36), complete transposition after Mustard's operation (n = 13), and tetralogy of Fallot (n = 13). Within 2 hours of bypass, both cardiac index and left ventricular stroke work index were adequate and increased appropriately with volume loading in all four diagnostic groups. The atrial septal defect group demonstrated a similar response to volume loading 4 and 24 hours after bypass. However, the other three diagnostic groups had a higher filling pressure, lower cardiac index and stroke work index, and a depressed response to increasing preload 4 hours postoperatively, which indicated a deterioration in cardiac performance. The deterioration was maximal between 4 and 12 hours after bypass, and performance tended to recover 24 hours postoperatively. The transposition group had a more profound depression in cardiac performance than the other two groups. Within the ventricular septal defect group, smaller children (body surface area less than 0.36 m2) had a more profound depression in performance than larger children. These results demonstrate a significant alteration in cardiac performance during the first 24 hours after repair of congenital cardiac defects in children. These changes should be considered when postoperative management is being planned.

Perioperative effects of alpha-stat versus pH-stat strategies for deep hypothermic cardiopulmonary bypass in infants.

OBJECTIVES: In a randomized, single-center trial, we compared perioperative outcomes in infants undergoing cardiac operations after use of the alpha-stat versus pH-stat strategy during deep hypothermic cardiopulmonary bypass. METHODS: Admission criteria included reparative cardiac surgery, age less than 9 months, birth weight 2.25 kg or more, and absence of associated congenital or acquired extracardiac disorders. RESULTS: Among the 182 infants in the study, diagnoses included D-transposition of the great arteries (n = 92), tetralogy of Fallot (n = 50), tetralogy of Fallot with pulmonary atresia (n = 6), ventricular septal defect (n = 20), truncus arteriosus (n = 8), complete atrioventricular canal (n = 4), and total anomalous pulmonary venous return (n = 2). Ninety patients were assigned to alpha-stat and 92 to pH-stat strategy. Early death occurred in four infants (2%), all in the alpha-stat group (p = 0.058). Postoperative electroencephalographic seizures occurred in five of 57 patients (9%) assigned to alpha-stat and one of 59 patients (2%) assigned to pH-stat strategy (p = 0.11). Clinical seizures occurred in four infants in the alpha-stat group (4%) and two infants in the pH-stat group (2%) (p = 0.44). First electroencephalographic activity returned sooner among infants randomized to pH-stat strategy (p = 0.03). Within the homogeneous D-transposition subgroup, those assigned to pH-stat tended to have a higher cardiac index despite a lower requirement for inotropic agents; less frequent postoperative acidosis (p = 0.02) and hypotension (p = 0.05); and shorter duration of mechanical ventilation (p = 0.01) and intensive care unit stay (p = 0.01). CONCLUSIONS: Use of the pH-stat strategy in infants undergoing deep hypothermic cardiopulmonary bypass was associated with lower postoperative morbidity, shorter recovery time to first electroencephalographic activity, and, in patients with D-transposition, shorter duration of intubation and intensive care unit stay. These data challenge the notion that alpha-stat management is a superior strategy for organ protection during reparative operations in infants using deep hypothermic cardiopulmonary bypass.

Transcranial Doppler monitoring of cerebral perfusion during cardiopulmonary bypass.

Profound hypothermic circulatory arrest and profound hypothermia with continuous low-flow cardiopulmonary bypass are used to facilitate repair of complex congenital heart lesions. Extended periods of profound hypothermic arrest may impair cerebral function and metabolism and produce ischemic brain injury. Low-flow bypass has been advocated as preferable to profound hypothermic arrest with respect to neurologic outcome as it maintains continuous cerebral circulation during repair of heart defects. Several studies have suggested that low-flow bypass produces equal degrees of cerebral injury as corresponding periods of circulatory arrest. Transcranial Doppler sonography has enabled the noninvasive study of cerebral perfusion during operations using either circulatory arrest or low-flow bypass. Although these studies have demonstrated the presence of cerebral perfusion at low perfusion pressures, evidence exists to suggest that cerebral perfusion abruptly ceases at cerebral perfusion pressures of 7 to 9 mm Hg and is unrelated to pump flow rate. Transcranial Doppler sonography is a useful tool for monitoring cerebral perfusion during low-flow bypass, and future studies with this modality may help to develop improved modes of cerebral protection during repair of complex congenital heart lesions.

The effect of low-flow cardiopulmonary bypass on cerebral function: an experimental and clinical study.

Systemic flow rates (Q) during nonpulsatile hypothermic cardiopulmonary bypass (CPB) that are consistent with preservation of cerebral function have not to our knowledge been objectively defined. The effect of a sequential reduction in flow rates on cerebral cortical metabolism and function was evaluated in 6 mongrel dogs during hypothermic (25 degrees C) CPB. Cerebral function was assessed using somatosensory cortical evoked potentials (SSEP); cerebral metabolism was assessed by adenosine triphosphate (ATP) and lactate content of snap-frozen gray matter biopsies taken from the hemisphere contralateral to that monitored for SSEP. A progressive decline in ATP levels was observed during flow reduction with virtually complete depletion of ATP at 0.25 L min-1 m-2(p = .0003). The significant (p = .028) dependence of cortical ATP levels on perfusion pressure was no longer evident after adjusting for the effects of flow rate. Lactate levels increased during flow reduction (p = .028), especially at flow rates less than 0.5 L min-1 m-2. Somatosensory neural transmission remained intact until flow was reduced to 0.25 L min-1 m-2 in 5 animals and until total circulatory arrest in 1, at which time loss of the signal occurred. In addition, 5 patients were subjected to brief periods of low-flow CPB (Q = 1.0 L min-1 m-2) at 21 degrees to 25 degrees C. SSEPs remained intact during flow reduction, and postoperative neurologic evaluation was normal in all patients. We conclude that, in the absence of cerebral vascular disease, the flow rate threshold for incurring functional cerebral injury during hypothermic (25 degrees C) nonpulsatile CPB is less than 1.0 L min-1 m-2.(ABSTRACT TRUNCATED AT 250 WORDS)

Expiratory muscle activity in anesthetized children: effect on the single breath technique.

Phasic expiratory activity of the abdominal muscles occurs in adults during halothane anesthesia, but has not been demonstrated in children. If present, abdominal muscle activity would preclude the use of recently developed tests of respiratory mechanics in children during anesthesia. We therefore measured abdominal muscle activity throughout induction of anesthesia with halothane in 10 patients between 1.5 and 9.5 years of age, seven with normal respiratory function and three with chronic airway obstruction. During induction of anesthesia with halothane in N2O and oxygen, the abdominal wall electromyograph (a-EMG) was continuously recorded from surface electrodes. At the same time, the expiratory time constant (tau a) was measured using the single breath test (SBT). The patients were then paralyzed with succinyl choline, and the a-EMG signal and expiratory time constant during paralysis (tau p) were recorded. The raw a-EMG signal and its moving time average were compared with the phase of respiration and with the end-tidal fraction of halothane (Fehalo), and the effect of abdominal muscle activity on tau a was noted. Of the 10 patients, 2 had no abdominal muscle activity at any time during induction. Of the remaining 8 patients, 3 had continuous abdominal muscle activity throughout induction, including one patient with asthma. In the remaining five patients, abdominal muscle activity was present during light halothane anesthesia and disappeared at increased Fehalo. When abdominal muscle activity was present, tau a was significantly less than tau p. It is concluded that abdominal muscle activity in expiration is undetectable during deep halothane anesthesia in most children.(ABSTRACT TRUNCATED AT 250 WORDS)

Physiologic dead space, venous admixture, and the arterial to end-tidal carbon dioxide difference in infants and children undergoing cardiac surgery.

End-tidal CO2 (PETCO2), arterial CO2 (PaCO2), mixed expired CO2 (PECO2), arterial and mixed venous oxygen contents were measured and the PaCO2 to PETCO2 difference (delta PCO2), physiologic dead space to tidal volume ratios (VD/VT) and venous admixture (Qs/Qt) were calculated in 41 anesthetized infants and children undergoing repair of congenital cardiac lesions. Eighteen children were acyanotic; 9 with normal pulmonary blood flow (PBF) and normal intracardiac anatomy (normal group); and 9 with increased PBF (acyanotic group). Twenty-three children were cyanotic; 14 with right to left intracardiac shunts and decreased PBF (cyanotic (D) group); and 9 with mixing lesions with normal or increased PBF (cyanotic (I) group). Correlations between PaCO2 and PETCO2 in the four groups of children were carried out and the relationship of delta PCO2 to VD/VT and Qs/Qt was determined. PETCO2 correlated closely with the PaCO2 in the normal and acyanotic groups (r2 = 0.97 and 0.91, respectively) and the lines of regression for the relationship between PaCO2 and PETCO2 for both groups did not differ from the line of identity (P less than or equal to 0.05). Mean +/- SD VD/VT for the normal and acyanotic groups were 0.35 +/- 0.17 and 0.39 +/- 0.19, respectively (NS). Corresponding values for the cyanotic (D) group and cyanotic (I) group were 0.38 +/- 0.16 and 0.55 +/- 0.16, respectively (NS), and were significantly greater than those from the normal and acyanotic groups (P less than 0.05). The relationship of delta PCO2 to VD/VT and Qs/Qt demonstrated that VD/VT was the most important determinant of delta PCO2, but in instances where Qs/Qt were large (e.g., cyanotic congenital heart disease) the percentage contribution of Qs/Qt to the delta PCO2 can be considerable.(ABSTRACT TRUNCATED AT 250 WORDS)

Anaesthetic management of the child with congenital heart disease for non-cardiac surgery.

CONCLUSION: Most children with congenital heart disease can be man-aged safely if the pathophysiology of their lesion and the anaesthetic implications are understood. However, recent reviews of anaesthetic morbidity reveal a high incidence of anaesthetic-related adverse events in children with congenital heart disease.

Anesthesia for cardiac surgery in neonates and infants.

The optimal management of neonates undergoing repair of complex congenital cardiac lesions requires detailed knowledge by the anesthesiologist of the anatomic and physiologic abnormalities and their consequences on the perioperative course. Management of these patients should not be undertaken in isolation but requires a concerted team approach for acceptable levels of mortality and morbidity to be obtained.

Anaesthetic implications of nemaline rod myopathy.

Nemaline rod myopathy is an inherited congenital myopathy first described in 1963. Affected patients characteristically present in infancy with a non-progressive hypotonia and symmetrical muscle weakness. The disease affects all skeletal muscles including the diaphragm with sparing of cardiac and other muscle. Facial dysmorphism is common as are skeletal deformities, including kyphosis, scoliosis and pectus excavatum. We present two sisters with nemaline rod myopathy and their anaesthetic management for scoliosis surgery. Facial dysmorphism was a feature of both cases. Preoperatively, both patients demonstrated poor respiratory function on pulmonary function testing. Both cases were successfully managed using controlled ventilation and inhalational anaesthetic agents, avoiding muscle relaxants. Postoperatively, there were no respiratory complications. Although one case report describes the use of succinylcholine and pancuronium in a patient with nemaline rod myopathy, we feel that neuromuscular blocking agents should be avoided where possible and only used with careful monitoring.

Cerebral blood flow velocity patterns during cardiac surgery utilizing profound hypothermia with low-flow cardiopulmonary bypass or circulatory arrest in neonates and infants.

To examine the effects of low-flow cardiopulmonary bypass (CPB) and circulatory arrest (PHCA) on cerebral pressure-flow velocity relationships, we studied 32 patients (< 9 mo of age) undergoing corrective cardiac procedures. Pressure-flow velocity relationships were studied during profound hypothermia (nasopharyngeal temperature < 20 degrees C). Cerebral blood-flow velocity (CBFV) was measured in the middle cerebral artery using transcranial Doppler sonography. The anterior fontanel pressure (AFP) was measured using an intracranial pressure monitor. Cerebral perfusion pressure (CPP) was calculated (mmHg) as mean arterial pressure (MAP) minus AFP. Nasopharyngeal temperature, PaCO2 and haematocrit were controlled during the study period. Alpha-stat acid-base management was employed. The CBFV measurements were made continuously over a range of CPP as pump flow (Q) was decreased to low-flow or to circulatory arrest and again during the subsequent increase in Q and CPP to normal. As Q and CPP were increased after a period of low-flow CPB during which period detectable CBFV was present, the CBFV was greater at any given CPP than prior to the low-flow state (P < 0.05). However, after PHCA a higher CPP (P < 0.05) was necessary to re-establish detectable CBFV and at any given CPP the CBFV was less than prior to PHCA (P < 0.05). Seventeen patients underwent low-flow CPB during which CBFV became non-detectable (7 +/- 1 cm.sec-1). In 12 of these patients the pattern of recovery of CBFV was the same as that observed after low-flow CPB whereas the remaining five (29%) demonstrated a pattern of recovery identical to the ones recorded after PHCA. We conclude that after PHCA a higher CPP is necessary to re-establish and maintain detectable CBFV. Furthermore, during low-flow CPB, patients where CBFV becomes non-detectable and show a pattern of CBFV recovery similar to PHCA, cessation of cerebral perfusion must be considered.

Stability of the intraoperative arterial to end-tidal carbon dioxide partial pressure difference in children with congenital heart disease.

The purpose of this study was to evaluate the stability of the arterial PCO2 (PaCO2) to end-tidal PCO2 (PETCO2) partial pressure difference (Pa-ETCO2) during surgery using PETCO2 monitoring, in children with congenital heart disease (CHD). Forty children with CHD were studied: ten children with no interchamber communication and normal pulmonary blood flow (PBF) (normal group); ten acyanotic children with increased PBF (acyanotic-shunting group); ten cyanotic children with mixing type lesions and normal or increased PBF (mixing group), and ten cyanotic children with right-to-left intracardiac shunts demonstrating decreased and variable PBF (cyanotic-shunting group). Simultaneous PaCO2 recordings and PETCO2 measurements were obtained for each patient during five intraoperative events: (1) control time, arterial line placement under anaesthesia; (2) time 1, patient preparation; (3) time 2, immediately after sternotomy; (4) time 3, after heparin administration; and (5) time 4, immediately after aortic cannulation. Initially, cyanotic children demonstrated a greater Pa-ETCO2 compared with acyanotic children (P less than 0.05). There was no difference in the Pa-ETCO2 over time in the control, acyanotic-shunting, or mixing groups. The Pa-ETCO2 in the children with cyanotic-shunting lesions at times 2 and 3 was greater (P less than 0.05) than at their control times. We conclude that the Pa-ETCO2 of children with acyanotic-shunting and mixing congenital heart lesions is stable intraoperatively, although patients with mixing congenital heart lesions may demonstrate large individual variations. In children with cyanotic-shunting congenital heart lesions, the Pa-ETCO2 is not stable. The PETCO2 cannot be used during surgery to estimate reliably the PaCO2 in children with cyanotic CHD.

Continuing medical education practices of community-based and university-affiliated anaesthetists in Ontario.

To remedy the lack of information about the continuing medical education (CME) practices of anaesthetists, we designed a survey to define and compare the CME activities of specialist anaesthetists in community-based and university-affiliated practices: 463 members of the Canadian Anaesthetists' Society in the Province of Ontario (263 community-based and 200 university-affiliated (University of Toronto) anaesthetists). Data from 304 (65.6%) respondents (172 community-based and 132 university-affiliated anaesthetists) were analyzed by non-parametric analysis (statistical significance P < 0.05). Most respondents spent between two to four hours per week on CME activities. Journal reading was the most commonly used method to obtain CME and was perceived to be the most efficient of the methods surveyed (P < 0.05). Formal teaching, including seminars, workshops, and annual society meetings, although the second most commonly used technique to obtain CME, was considered as effective as journal reading. Instructional media techniques were the least commonly used and considered the least effective (P < 0.05). Most community-based and university-affiliated anaesthetists obtained CME by a variety of techniques; of all respondents, 77% have no formal method of assessing their learning needs and 88% would consider participation in a formalized learning needs assessment programme.