Current concepts in brain resuscitation.

In spite of the tremendous amount of effort and money put forth to reduce morbidity and mortality associated with global cerebral ischemia, the outlook for patients suffering an ischemic insult remains dismal. The lack of a sufficient substrate supply during the period of ischemia as well as the production of toxic metabolites in response to ischemia have been incriminated as key factors causing brain damage. As discussed in this article, modes of therapy have included efforts to minimize the duration of ischemia (eg, effective cardiopulmonary resuscitation, hemodilution, heparinization, calcium antagonists) and decrease the production of toxic metabolites (eg, barbiturates, calcium antagonists). Although the barbiturates have also been proposed to decrease the metabolic needs during ischemia, they have no therapeutic value for global cerebral ischemia. The initial evaluation of the calcium antagonists has been more promising.

Utilizing functional lumen imaging probe topography to evaluate esophageal contractility during volumetric distention: a pilot study.

BACKGROUND: The functional lumen imaging probe (FLIP) measures luminal cross-sectional area and pressure during volumetric distension. By applying novel customized software to produce FLIP topography plots, organized esophageal contractility can be visualized and analyzed. We aimed to describe the stimulus thresholds and contractile characteristics for distension-induced esophageal body contractility using FLIP topography in normal controls. METHODS: Ten healthy controls were evaluated during endoscopy with FLIP. During stepwise bag distension, simultaneous intra-bag pressure and luminal diameter measurements were obtained and exported to a MatLab program to generate FLIP topography plots. The distension volume, intra-bag pressure, and maximum esophageal body diameters were measured for the onset and cessation of repetitive antegrade contractions (RACs). Contraction duration, interval, magnitude, and velocity were measured at 8 and 3-cm proximal to the esophagogastric junction. KEY RESULTS: Eight of ten subjects demonstrated RACs at a median onset volume of 29 mL (IQR: 25-38.8), median intra-bag pressure of 10.7 mmHg (IQR: 8.6-15.9), and median maximum esophageal body diameter of 18.5 mm (IQR: 17.5-19.6). Cessation of RACs occurred prior to completion of the distension protocol in three of the eight subjects exhibiting RACs. Values of the RAC-associated contractile metrics were also generated to characterize these events. CONCLUSIONS & INFERENCES: Distension-induced esophageal contractions can be assessed utilizing FLIP topography. RACs are a common finding in asymptomatic controls in response to volume distention and have similar characteristics to secondary peristalsis and repetitive rapid swallows.

Gonadotropin-releasing hormone axons target the median eminence: in vitro evidence for diffusible chemoattractive signals from the mediobasal hypothalamus.

The projection of GnRH neurons to the median eminence of the medial basal hypothalamus (MBH) is established early in development and is also seen when preoptic area-derived GnRH cell-containing grafts are placed in the third ventricle of hypogonadal mice. To further study the factors directing GnRH axonal targeting, we cultivated embryonic or postnatal day 1 preoptic area with a coexplant on collagen- and laminin-coated membranes in insert chambers. After 7 days of culture, GnRH-immunoreactive fibers extended significantly farther and in greater number onto the sector of membrane facing a MBH coexplant than in the opposite sector, but not toward coexplants of control tissue. Moreover, such effects were specific, as outgrowth of a general axonal population, immunoreactive for growth-associated protein 43 was not influenced by the presence of the MBH. Preferential GnRH outgrowth toward the MBH was established early and was maintained during 10 days of culture. The importance of substrate-derived guidance was also assessed with confocal microscopy. GnRH axons consistently traveled in the company of growth-associated protein 43-labeled axons, but only erratic associations were seen between GnRH and glial processes extending on the membrane. We suggest that although employing an axonal substrate, GnRH axons follow a diffusible chemoattractive signal(s) secreted by the MBH.

Comparison of cerebrovascular response to hypoxic and carbon monoxide hypoxia in newborn and adult sheep.

Cerebral blood flow (CBF) responses to two types of isocapnic hypoxia, hypoxic hypoxia (HH) and carbon monoxide hypoxia (COH), were examined in seven unanesthetized adult sheep by the radiolabeled microsphere technique. Comparisons were made with newborn lambs (5-12 days old) previously studied under similar conditions. The arterial O2 content (CaO2) was reduced in a graded manner to 50-60% of the control value. During HH, CBF increased to maintain cerebral O2 delivery (CaO2 X CBF) in both adults and newborns; however, cerebral O2 uptake (CMRO2) did not change. Although CMRO2 was higher in newborns, the responses of CBF/CMRO2 to HH did not differ significantly in newborns and adults. In newborns, regional CBF showed that brainstem areas were particularly responsive to HH. In both age groups, CBF increased to a greater extent with COH than with HH for similar reductions in CaO2. This resulted in an increase in cerebral O2 delivery with COH. The degree to which COH differed from HH correlated with the magnitude of the leftward shift of the oxyhemoglobin dissociation curve that accompanies COH. In adults, CMRO2 fell by 16% with COH but was maintained in newborns. We conclude that maintenance of cerebral O2 delivery during acute, isocapnic HH is a property of CBF regulation common to both newborn and adult sheep. During COH, the position of the oxyhemoglobin dissociation curve is an additional factor that sets the level of O2 delivery. The fetal conditions of low CaO2 and a left-shifted oxyhemoglobin dissociation curve may have provided the newborn with a microcirculation better suited for maintaining CMRO2 during COH.

Gypsies and acute medical intervention.

Recently, a 7-month-old, terminally ill Gypsy infant was admitted to a pediatric intensive care unit. Treating this child and her extended family was a challenging experience during which numerous culture-related problems were encountered. The Gypsy approach to acute medical care consisted of the presence of a large extended family unit, the lack of decision making by the patient's parents, and several different Gypsy traditions. There were diverse, and often derogatory, reactions and prejudices from the hospital staff. After interviewing family members, this family's needs were easier to understand, and interaction with them in culturally relevant terms was possible. When dealing with Gypsy families, identification of the responsible elder male members of the family, establishment of firm lines of communication with essential family members and the parents, and education of the medical staff concerning Gypsies are recommended.

Cerebral blood flow measurement techniques in infants and children.

The tremendous growth of interest in neurologic intensive care and in the pathophysiology of the cerebral circulation in the past few years has resulted in increasing numbers of studies that document alterations in cerebral flow during the course of various diseases or as a response to treatment of them. Before pediatricians come to conclusions based on these studies, it is important to have an understanding of the techniques involved. The techniques are complex and difficult but are based on understandable principles. They also have limitations and are subject to misinterpretations. Pediatricians should become knowledgeable about some of these techniques and their limitations because it is likely that they will be applied with increasing frequency in the next several years. We are on the threshold of exciting discoveries in abnormalities of cerebral blood flow and cerebral metabolism not only in critically ill children but also in children with congenital and learning disorders.

Prevention of apnea and bradycardia in low-birthweight infants.

The efficacy of theophylline in preventing severe apnea was evaluated in 17 low-birthweight infants (mean weight, 1,400 gm). Apnea was detected and accurately quantified by 13-hour pneumogram recordings and correlated with serum theophylline levels. Nursing observations coupled with on-line alarm systems detected only 39% of severe apneic episodes as compared to the pneumogram recording technique. Theophylline in six hourly oral doses(1.5 to 4.0 mg/kg) yielded two-hour serum concentrations of 6.6 to 11.0 mug/ml which completely controlled apneic spells exceeding 20 seconds in duration and markedly reduced 10- 19-second apneic episodes and any resultant bradycardia. At these serum levels, toxicity was not observed. Therapy with theophylline should be instituted at a dose of 2 to 3 mg/kg every six hours and the optimum therapeutic dose should be individualized as determined by objective quantitation of apnea and serum theophylline concentration.

Long-term outcome of children with severe head trauma and prolonged coma.

Forty-six children with significant head trauma who remained in coma more than 24 hours were the subjects of this long-term outcome study. Twelve (38%) died. The average length of coma in the 34 survivors was 15.5 days. Follow-up ranged from 9 months to 4 years (mean 21 months). Twenty-nine percent of the survivors were normal at follow-up. An additional 53% had mild cognitive or behavioral problems, but 61% of these had evidence of similar problems prior to the injury. Nine percent of survivors had motor residua but normal intellect. Nine percent had severe intellectual and motor problems. Children less than 2 years of age had a worse outcome. Despite severe injury and prolonged coma after head trauma, most children do well. Intensive medical and surgical care increases the rate of survival and does not result in a large number of severely disabled survivors.

Intensive management of severe head injury.

Intensive management of patients with severe head injury offers the best hope of minimizing death and functional disability in a young, working population. Secondary neurologic insult can be decreased by cardiorespiratory support and ICP control from the outset. Rapid neurologic assessment, airway management, and support of circulation are the basis of emergency management for head injury. Patients with severe head injury require intensive care management for two major reasons: management of ICP and management of organ system dysfunction. Care should not be withheld because of initially grim (and inaccurate) prognostic assessment. Newer techniques for assessing the adequacy of cerebral circulation may allow refinement of management strategies in the future.

The physiology of cardiopulmonary resuscitation.

As the pathophysiology of CPR is understood, ways to alter cerebral blood flow and neurologic outcome following CPR are likely to develop. This review highlights those areas likely to be of clinical importance in the near future.

O2 radicals mediate reperfusion lung injury in ischemic O2-ventilated canine pulmonary lobe.

This study was undertaken to determine whether lung injury after a period of ischemia reperfusion is caused by O2 ventilation during ischemia and whether this injury is mediated by reactive O2 metabolites. Isolated canine left lower pulmonary lobes were subjected to room temperature ischemia for 6 h while being ventilated with either 100% O2, room air, or 100% N2. After the ischemic period, all lobes were perfused with autologous blood and ventilated with 100% O2 for an additional 4 h. In lobes ventilated with 100% O2 during the ischemic period, massive weight gain (228%) occurred 4 h after reperfusion. A marked increase in pulmonary shunt was noted. Lobes ventilated with room air behaved similarly. In contrast, lobes ventilated with 100% N2 gained significantly less weight (54%) and did not manifest any increase in pulmonary shunt. When lobes ventilated with 100% O2 or room air were pretreated with superoxide dismutase (SOD), the injury was significantly reduced. Pressure-volume deflation study of lobes, after ischemia only, demonstrated that ventilation with 100% O2 and with 100% N2 both equally decreased pulmonary compliance. We conclude that lung ischemia-reperfusion injury is related to O2 ventilation during ischemia and that injury can be prevented by administration of SOD or ventilation with 100% N2. This suggests that the injury is related to O2 metabolites produced during O2 ventilation in the absence of the circulation.

Age-related changes in chest geometry during cardiopulmonary resuscitation.

We studied alterations of chest geometry during conventional cardiopulmonary resuscitation in anesthetized immature swine. Pulsatile force was applied to the sternum in increments to determine the effects of increasing compression on chest geometry and intrathoracic vascular pressures. In 2-wk- and 1-mo-old piglets, permanent changes in chest shape developed due to incomplete recoil of the chest along the anteroposterior axis, and large intrathoracic vascular pressures were generated. In 3-mo-old animals, permanent chest deformity did not develop, and large intrathoracic vascular pressures were not produced. We propose a theoretical model of the chest as an elliptic cylinder. Pulsatile displacement along the minor axis of an ellipse produces a greater decrease in cross-sectional area than displacement of a circular cross section. As thoracic cross section became less circular due to deformity, greater changes in thoracic volume, and hence pressure, were produced. With extreme deformity at high force, pulsatile displacement became limited, diminishing pressure generation. We conclude that changes in chest geometry are important in producing intrathoracic intravascular pressure during conventional cardiopulmonary resuscitation in piglets.

Age-related effects of compression rate and duration in cardiopulmonary resuscitation.

The effects of various compression rate and duration combinations on chest geometry and cerebral perfusion pressure during cardiopulmonary resuscitation (CPR) were studied in immature swine. Pentobarbital-anesthetized 2- and 8-wk-old piglets received CPR after ventricular fibrillation. At compression rates of 40, 60, 80, 100, 120, and 150/min, duty cycle (compression duration/total cycle time) was increased from 10 to 80% by 10% increments. Mean aortic and sagittal sinus pressures, pulsatile displacement, and deformity of the anterior chest wall were measured. Increasing duty cycle increased cerebral perfusion pressure until chest relaxation time was compromised. Inadequate chest recoil, development of static chest deformation, and limitation of pulsatile chest wall movement occurred in both age groups when relaxation time was very short (150-200 ms in 2-wk-old piglets, 250-300 ms in 8-wk-old piglets). These changes in chest geometry correlated with deterioration of cerebral perfusion pressure only in 8-wk-old piglets. In the younger group, perfusion pressures plateaued but did not deteriorate. These data emphasize the importance of duty cycle in generating cerebral perfusion pressure and indicate that younger animals can tolerate high compression rates except at extremely long duty cycles.

Cerebral vascular diseases.

Strokes remain an important cause of mortality and morbidity despite recent advances in neurologic intensive care. Although support of ventilation and circulation improves the outcome for stroke patients, the efficacy of cerebral resuscitative measures such as hyperventilation, osmotherapy, fluid restriction, steroids, intracranial pressure control, and barbiturates remains unproven. Current specific therapies (anticoagulation, surgery) are useful in carefully selected patients. New therapies now being researched include fluorocarbons, narcotic antagonists, and calcium blockers.

An overview of the intracranial vault. Physiology and philosophy.

This overview of the intracranial vault from a physiologic and philosophic basis should set the stage for a critical analysis of the contents of this volume. There is much to be taught in this area but even more to be learned.

Fulminant hepatic failure and hepatic encephalopathy.

Fulminant hepatic failure implies either acute massive destruction of liver tissue or another process that causes rapid deterioration in function of a previously normal liver. The diagnosis in children needs to be differentiated from hepatic failure that occurs as a complication of underlying congenital, anatomical, and metabolic abnormalities.

Intracranial pressure monitoring in the management of the pediatric trauma patient.

Intracranial pressure (ICP) monitoring is an important adjunct in the management of the severely injured child with major head trauma. From a series of 18 patients with multiple trauma, smoke inhalation, and near-drowning, we report an illustrative case of head injury and pulmonary aspiration in which ICP monitoring was vital to appropriate therapy. The two most common techniques of ICP monitoring, the intraventricular catheter and the subarachnoid bolt, are described. Treatment of intracranial hypertension is discussed based on physiological principles. The continuous, objective recording of ICP assumes particular importance when therapy directed at other injured organ systems (ie, institution of positive end-expiratory pressure) could adversely affect the ICP. It is suggested that optimal care of children with multiple trauma and head injury include early ICP monitoring.

Behavioral assessment for pediatric intensive care units.

Two studies were conducted to analyze behaviors of staff and patients on a Pediatric Intensive Care Unit (PICU). In the first study, behavioral observation procedures were employed to assess patient state, physical position, affect, verbal behaviors, visual attention and activity engagement, and staff verbal behavior. On the average, one-third of the patients were judged to be conscious and alert but markedly nonengaged with their environment. In the second study, a member of the hospital staff provided alert patients with individual activities to determine whether a simple environmental manipulation could positively affect behavior of children in intensive care. Employing a reversal design, the activity intervention was found to increase attention and engagement and positive affect, and to decrease inappropriate behavior. Both studies demonstrate that behavioral assessment procedures can provide an empirical basis for designing PICU routines affecting children's psychosocial status, and, thus, complement current procedures designed to provide quality medical care.