Steven L. Wald

The effect of hypotension and hypoxia on children with severe head injuries

Survival of children (< 17 years) with severe head injuries (Glascow Coma Scale [GCS] score < 8) has been shown to be better than that of adults. The addition of hypotension (HT) or hypoxia (H) has a deleterious effect on outcome in adults but no information is currently available about their effects in children. Over a 5-year period, 58 children with GCS scores < 8 were admitted and prospectively evaluated at this institution. Patients were divided into two groups on the basis of systolic blood pressure (SBP) and arterial blood gasses. Patients exhibiting HT, defined as a SBP < 90 mm Hg, and patients demonstrating H with a PaO2 < 60 mm Hg were compared with normoxic, normotensive children. Survival was increased fourfold in patients with neither H nor HT as compared with children with either H or HT (P < .001). To validate these observations we reviewed the data from the National Pediatric Trauma Registry for similar patients and included our cohort in the analysis. In total, 509 children had sufficient data for analysis and were studied. Hypoxia alone was not associated with increased mortality in normotensive patients (P = .34). Hypotension significantly increased mortality in these children even without concomitant H (P < .00001). If both HT and H were found together, mortality was only slightly increased over those children with HT alone (P = .056). These data confirm that HT with or without H causes significantly increased mortality in head-injured children to those levels normally found in adults (P = .9), alleviating any age-related protective mechanisms normally afforded.(ABSTRACT TRUNCATED AT 250 WORDS)

The Deleterious Effects Of Intraoperative Hypotension On Outcome In Patients With Severe Head Injuries

Prehospital or admission hypotension doubles the mortality for patients with severe head injury (SHI = Glasgow Coma Scale score less than or equal to 8). To our knowledge no study to date has determined the effects of intraoperative hypotension [IH: systolic blood pressure (SBP) less than 90 mm Hg] on outcome in patients with SHI. This study examined 53 patients who had SHI and required early surgical intervention (surgery within 72 hours of injury). All patients were initially normotensive on arrival. There were 17 patients (32%) who developed IH and 36 (68%) who remained normotensive throughout surgery. The mortality rate was 82% in the IH group and 25% in the normotensive group (p less than 0.001). The duration of IH was inversely correlated with Glasgow Outcome Scale using linear regression (R = -0.30; p = 0.02). Despite vigorous fluid resuscitation in the IH group, additional pharmacologic support was used in only 32%. These data suggest that IH is not uncommon after SHI (32%) and that it does have a significant effect on patient outcome.

The Effect Of Secondary Insults On Mortality And Long-term Disability After Severe Head Injury In A Rural Region Without A Trauma System

Outcome after head injury appears to be adversely affected by secondary insults such as hypoxia or hypotension. Previous work examining the influence of these secondary insults on outcome has originated from urban environments with organized systems of trauma care. We hypothesized that secondary insults would be more frequent and that outcome of severe head injury would be worse in a rural region without a trauma system. To validate these hypotheses we retrospectively reviewed the course and outcome of all patients admitted to the Medical Center Hospital of Vermont with severe head injuries between 1980 and 1985. A cohort of 170 patients was assigned to one of two groups: group I had neither hypotension nor hypoxia at the time of admission; group II had either hypotension or hypoxia at the time of admission. The groups were similar in terms of demographics, incidence of mass lesions, frequency of craniotomy, and incidence of intracranial hypertension. Only 23% of group II patients made a good recovery compared with 56% of group I patients (p < 0.01). The mortality rate of group II patients was twice that of group I patients (66% vs. 33%; p < 0.01). When compared with data provided by the National Trauma Coma Data Bank from urban areas with trauma systems, there was no difference in outcome of patients similarly grouped according to the presence or absence of secondary insults between Vermonts rural cohort and the urban cohort. We conclude that hypotension and hypoxia adversely effect the outcome of severe head injury.(ABSTRACT TRUNCATED AT 250 WORDS)

Computed tomographic angiography as a screening modality for blunt cervical arterial injuries: preliminary results.

BACKGROUND The diagnosis of blunt cervical arterial injury (CAI) is made difficult by its infrequent occurrence and delayed presentation. Beginning in January of 1995, we used computed tomographic angiography (CTA) of the neck to screen for CAI. We hypothesized that CTA could be incorporated into the workup of patients sustaining blunt neck injury as a screening modality for CAI and that CTA would increase the early detection of CAI. METHODS Retrospective review of all CAI for the years January of 1988 to June of 1997 at a Level I trauma center. CAI diagnosed before introduction of CTA (pre-CTA; January of 1988 to December of 1994) were compared with those after (post-CTA; January of 1995 to June of 1997). RESULTS The overall incidence of CAI for the entire time period was 0.11%. Motor vehicle crash (53%) was the most common mechanism, with focal neurologic deficit (23%) or seizures (17.6%) the most common presenting clinical symptoms. CTA added only a few additional minutes to the time required for the workup of patients sustaining blunt neck injury in whom CAI was suspected. The incidence of CAI increased from 0.06% pre-CTA to 0.19% post-CTA (p = 0.02; Fisher exact test). CTA was associated with a decrease in mean time to make the diagnosis of CAI (156 hours pre-CTA vs. 5.9 hours post-CTA). In addition, CTA was associated with a decrease in the incidence of permanent neurologic sequelae from CAI (50% pre-CTA vs. 0% post-CTA; p = 0.07; Fisher exact test). CONCLUSION We conclude that CTA does not significantly increase the time of the diagnostic workup of the patient with injuries caused by blunt trauma. The introduction of CTA at our institution was associated with an increase in the detection rate of CAI. Earlier detection of CAI may allow for more timely therapeutic intervention and potentially prevent permanent neurologic sequelae.

Pediatric blunt carotid injury: a review of the National Pediatric Trauma Registry.

Blunt carotid injury (BCI) is an uncommon yet potentially devastating entity which has received little attention in the pediatric literature. In an attempt to better characterize pediatric BCI, a review of the National Pediatric Trauma Registry was performed. Records were obtained from all children diagnosed with internal or common carotid injury associated with blunt trauma. The incidence of BCI was 0.03% (15 of 57,659 blunt trauma patients). Variables examined included: age, gender, mechanism of injury, associated injuries, various injury severity scores, and outcome. Various injuries were associated with an increase in BCI incidence including chest trauma (4-fold), combined head and chest trauma (6-fold), basilar skull fractures (4-fold), intracranial hemorrhage (6-fold), and clavicle fractures (8-fold). Thirty-three percent of the patients diagnosed with BCI suffered neurological complications directly attributable to their carotid injuries. Current practices regarding screening, diagnosis, and treatment are reviewed.

Prophylactic vena cava filter insertion in patients with traumatic spinal cord injury: preliminary results.

Pulmonary embolism (PE) is a devastating complication in patients with traumatic spinal cord injury (SCI). Prophylactic measures such as venous compression hose or low-dose heparin are only partially protective in reducing the risk of venous thromboembolism and are contraindicated in some patients. Because of extended perturbations in fibrinolytic activity, catecholamine effects on platelet aggregation, increased activity of complement and acute phase reactants, abnormally high factor VIII concentrations, and persistent venous stasis with ongoing endothelial damage, the patient with an SCI remains at prolonged risk for venous thromboembolism. A retrospective 5-year review at the Medical Center Hospital of Vermont revealed seven patients with eight documented PEs (three fatal; 2.7%) in 111 SCI patients (6.3%). Six PEs (75%) occurred after discharge from the acute care facility. Median time to PE after injury was 78 days (range, 9-5993). Although comprising only 4% of all trauma admissions, SCI accounted for 31% of all PEs in the total trauma population (2525 patients). Beginning in July 1991, a new prophylaxis protocol was instituted, which included the percutaneous insertion of vena cava filters under local anesthesia in all SCI patients with paraplegia or quadriplegia. Fifteen patients have undergone the insertion of titanium filters. Impedance plethysmography was performed weekly to detect deep venous thrombosis. No complications were associated with vena cava filter insertion. No patients developed deep venous thrombosis during their acute hospitalization (median, 22 d), and no patients have developed PE after filter insertion.(ABSTRACT TRUNCATED AT 250 WORDS)

Multiple head injuries in rats: Effects on behavior

BACKGROUND Evidence suggests that mild head injuries in humans can result in cumulative damage. No investigation to date has considered the effects of multiple subacute mild head injuries in an animal model. METHODS Forty-one male Long-Evans hooded rats were trained in a Morris water maze. All animals were fitted with a hollow intracranial screw. Concussions were generated using a fluid percussion device. Animals were then evaluated in the water maze until performance returned to baseline. Control animals received no concussions. The remaining animals were randomized to receive one, two, or three concussions. Animals were allowed to return to baseline after each concussion and were then killed. Motor performance was evaluated on a balance beam both before and after concussions. RESULTS After one concussion, 85% of animals showed performance deviation from baseline as measured by time to reach the platform, returning to baseline within a mean of 14.0 trials. After two concussions, 48% of animals showed deviation, with a mean return to baseline of 6.8 trials. After three concussions, 25% of animals showed deviation, with a mean return to baseline of 2.3 trials. Of postconcussive animals, 42% developed new inconsistent baseline levels of performance. Balance beam performance was unaffected. CONCLUSION Multiple concussions cause immediate transient impairment in spatial recognition and have extended effects on baseline performance in rats. Motor performance is not affected.

An analysis of the relationship between fluid and sodium administration and intracranial pressure after head injury

Severe head injury is the leading cause of traumatic death. When a severe head injury is combined with hypotension the mortality doubles. The use of asanguineous salt solutions to maintain blood pressure, however, may contribute to cerebral swelling and intracranial hypertension. For this reason, restrictions of fluids (FLD) and sodium (Na) have been advocated. To our knowledge, however, there are no clinical data to support this recommendation. We hypothesized that in adult patients sustaining severe head injuries (Glasgow Coma Scale score less than or equal to 8) with or without associated injuries: (1) FLD balance and total Na administered during the initial 72 hours of hospital admission are positively and significantly correlated with each other, and (2) total FLD, FLD balance, and total Na administration during the initial 72 hours are significantly and positively correlated with changes in ICP and adverse outcome. We retrospectively studied 40 adult trauma patients with severe head injuries. We found a significant correlation between total Na and FLD balance (R2 = 0.54; p less than 0.05). However, we found no significant correlation between total FLD and maximum ICP (R2 = 0.081), ICP score (R2 = 0.01), or outcome (R2 = 0.066), no significant correlation between FLD balance and maximum ICP (R2 = 0.000), ICP score (R2 = 0.000), or outcome (R2 = 0.01), and no significant correlation between total Na and maximum ICP (R2 = 0.000), ICP score (R2 = 0.001), or outcome (R2 = 0.02). We conclude that Na and FLD administration are not independent determinants of ICP during the initial 72 hours after brain injury.

Synergistic Action of Genistein and Cisplatin on Growth Inhibition and Cytotoxicity of Human Medulloblastoma Cells

Objective: Recent experimental data have shown that dietary soy isoflavones such as genistein can significantly suppress invasiveness and growth of a number of human malignancies. In this study we examined whether genistein, at a concentration typical of plasma levels following soy formula intake, in combination with cisplatin or vincristine exhibited an additive or synergistic inhibitory effect on the growth of medulloblastoma cells. Methods: Three human medulloblastomas cell lines (HTB-186, CRL-8805 and MED-1) were treated with genistein at 6 μM, the maximum reported dietary plasma level in children, combined with cisplatin (0–10 μM) or vincristine (0–1 μM). Monolayer cell growth and cytotoxicity, as measured by colonigenic survival in soft agarose, were then compared in control and drug-treated cultures. Presence of apoptosis, using the DNA ladder assay and laser scanning cytometry, was investigated in all cell lines at those concentrations at which an enhancement of antiproliferative effect of cisplatin and vincristine in presence of genistein was observed. Results: Genistein at 6 μM led to a 2.8-fold increase in the monolayer growth inhibitory effect of cisplatin (0.05 μM) in HTB-186 cells (p = 4.5 × 10–4 by one-tailed t test). Genistein increased colonigenic survival inhibition of HTB-186 2.6-fold at the same cisplatin concentration (p = 1.5 × 10–4). Genistein caused a 1.3-fold increase in antiproliferative effect of cisplatin (0.5 μM) in CRL-8805 cells (p = 3.1 × 10–4). Similarly the inhibition of colonigenic survival was enhanced 2.0-fold in CRL-8805 (p = 1.22 × 10–5). The addition of genistein to 0.5 μM cisplatin led to a 1.7-fold increase in monolayer growth inhibition and 2.4-fold increase in colonigenic survival inhibition of MED-1 cells (p = 8.3 × 10–4 and p = 1.1 × 10–4 respectively). These effects were primarily synergistic but also additive in nature. The combination of genistein and vincristine, as compared to vincristine alone, caused a minimal-to-modest increase in antiproliferative effect on medulloblastoma cells studied here. We were unable to detect apoptosis by two methodologies in any of the medulloblastoma lines when genistein was combined with cisplatin or vincristine. Conclusion: These results indicate that genistein at typical dietary plasma levels can significantly enhance the antiproliferative and cytotoxic action of cisplatin and, to a lesser extent, vincristine. The implication for treatment of medulloblastomas of early childhood may be a reduction in the chemotherapeutic dose recommendations of these agents and subsequently a decrease in the risk of treatment sequelae for these patients.

Prophylactic Vena Cava Filter Insertion in Patients with Traumatic Spinal Cord Injury

Pulmonary embolism (PE) is a devastating complication in patients with traumatic spinal cord injury (SCI). Prophylactic measures such as venous compression hose or low-dose heparin are only partially protective in reducing the risk of venous thromboembolism and are contraindicated in some patients. Because of extended perturbations in fibrinolytic activity, catecholamine effects on platelet aggregation, increased activity of complement and acute phase reactants, abnormally high factor VIII concentrations, and persistent venous stasis with ongoing endothelial damage, the patient with an SCI remains at prolonged risk for venous thromboembolism. A retrospective 5-year review at the Medical Center Hospital of Vermont revealed seven patients with eight documented PEs (three fatal; 2.7%) in 111 SCI patients (6.3%). Six PEs (75%) occurred after discharge from the acute care facility. Median time to PE after injury was 78 days (range, 9-5993). Although comprising only 4% of all trauma admissions, SCI accounted for 31% of all PEs in the total trauma population (2525 patients). Beginning in July 1991, a new prophylaxis protocol was instituted, which included the percutaneous insertion of vena cava filters under local anesthesia in all SCI patients with paraplegia or quadriplegia. Fifteen patients have undergone the insertion of titanium filters. Impedance plethysmography was performed weekly to detect deep venous thrombosis. No complications were associated with vena cava filter insertion. No patients developed deep venous thrombosis during their acute hospitalization (median, 22 d), and no patients have developed PE after filter insertion.(ABSTRACT TRUNCATED AT 250 WORDS)