Worsening Of Outcomes Research Articles

Decitabine (DAC) Can Be Safely Reduced After Achievement of Best Response In Patients (pts) with Myelodysplastic Syndrome (MDS)

AbstractAbstract 1858DAC is standard therapy in pts with MDS. Current recommendations suggest a dose of 20 mg/m2 IV daily for 5 days every 4 weeks for as many cycles as possible to secure the best outcome. However, this therapy is associated with frequent grade 3–4 hematologic toxicity, requiring dose reduction (DR) and frequent dose delay (DD). We investigated the outcome of pts who had DD/DR and whether the timing of this dose modification relative to the time of response is relevant. Pts enrolled in phase II trials using DAC for frontline therapy for MDS were analyzed: 124 pts were treated at the dose of 10 mg/m2 IV daily × 10 days (n=17), 20 mg/m2 subcutaneously daily × 5 days (n=14), and 20 mg/m2 IV daily × 5 days (n=93). Median age was 65 years (range 37–90). Median follow up was 48 months. Seventy six pts responded, with 54 (44%) achieving a complete response (CR), 5 (4%) marrow CR, and 17 (14%) clinical benefit. The median transformation free survival (TFS) and overall survival (OS) was 13 and 20 months, respectively. Responders had better performance status (p=0.015), better baseline hemoglobin (p=0.006) and lower baseline blast percentage (p=0.05) than non responders. Sixty five pts (53%) had DR by at least 25% or DD (defined by a delay beyond 5 weeks between cycles) for a median of 7 days (range, 1 to 97), 25 had both. The main reasons for DR/DD were myelosuppression in 48 pts (74%) and infection in 10 pts (15%). Pts with DD/DR were more likely to have diploid cytogenetics (p=0.001) and received more DAC cycles (4 versus 11; p=0.001). There were no other statistically significant differences in characteristics between pts who had DD/DR versus those who did not. DD occurred after a median of 2 courses, with a median of 4 delays per pt (range, 1 to 22). DR occurred after a median of 7 courses (range, 2 to 24) with a median reduction of 25%. The median number of courses with DR was 6 (range, 1 to 18). Thirty five pts (54%) underwent DD/DR after achieving an objective response including 27 (42%) after CR. There was a trend for more durable responses in favor of pts requiring DD/DR after the achievement of an objective response (median not reached) compared to those who required DD/DR before (median of 18 months) (p=0.5). The 2-year OS rate trended higher for pts who had DD/DR after obtaining best response compared to those who had DD/DR prior to best response. The median OS was 30 and 22 months, respectively (p=0.15). There was no worsening in outcome when comparing pts who had no DD/DR to those who had DD/DR after the achievement of an objective best response. Transformation free survival (TFS) rates also trended higher for those with DD/DR after response compared to those who required DD/DR before. The median TFS was 27 and 18 months, respectively (p=0.12).In conclusion, DAC is effective in treating pts with MDS; DD/DR can be safely accomplished once the pt has achieved the best objective response (preferably CR) without impacting outcome. Prospective evaluation of an approach conceiving a loading dose for induction of a best objective response followed by a maintenance schedule is to be considered. Disclosures:Ravandi:Eisai: Honoraria, Research Funding. Cortes:Eisai: Research Funding.

Exacerbation of systemic inflammation and increased cerebral infarct volume with cardiopulmonary bypass after focal cerebral ischemia in the rat

Stroke remains a significant contributor to morbidity and mortality after cardiac surgery. Cardiopulmonary bypass is known to induce a significant inflammatory response, which could adversely influence outcomes. We hypothesized that cardiopulmonary bypass, through an enhanced systemic inflammatory response, might affect outcomes after focal cerebral ischemia. Wistar rats (275-300 g) were anesthetized, surgically prepared for cardiopulmonary bypass and right middle cerebral artery occlusion, and randomly allocated to 2 groups: focal cerebral ischemia alone (n = 9) and focal cerebral ischemia combined with normothermic cardiopulmonary bypass (n = 8). Serum cytokines (tumor necrosis factor alpha and interleukins 1beta, 6, and 10) were measured at baseline, at end of bypass, and at 2, 6, and 24 hours after bypass. On postoperative day 3, animals underwent neurologic testing, after which the brains were prepared for assessment of cerebral infarct volume. Data were compared between groups by Mann-Whitney U test. Compared with the ischemia-alone group, the ischemia plus bypass group had significantly higher levels of circulating tumor necrosis factor alpha and interleukins 1beta and 10 at the end of bypass and 2 hours after bypass. In addition, the ischemia plus bypass animals had larger total cerebral infarct volumes (286 +/- 125 mm(3)) than did those with ischemia alone (144 +/- 85 mm(3), P = .0124). Cardiopulmonary bypass increased cerebral infarct size after focal cerebral ischemia in rats. This worsening of outcome may in part be related to an augmented inflammatory response that accompanies cardiopulmonary bypass.

Early Surgery Is Recommended for Mitral Regurgitation

Mitral regurgitation (MR), the systolic flow reversal from the left ventricle to the left atrium, is currently the most frequent valvular heart disease.1 Because MR affects predominantly patients ≥65 years of age,1 with age at surgery most often in the sixth decade,2 the observed prevalence will increase with the aging of the population. Thus, the number of US citizens affected by moderate or severe MR will almost double between 2000 and 2030, reaching almost 5 million by then.1 MR mechanism is classified as organic (intrinsic valve lesions) or functional (structurally normal mitral valve with MR caused by ventricular dysfunction).3 Indications of mitral surgery, the only current approved treatment of MR, are disputed because large clinical trials in MR have not been reported and outcome studies provide the best evidence available but require careful interpretation. The benefit of surgery is uncertain in functional MR and is not addressed here.4 However, we illustrate here that overwhelmingly coherent cumulative evidence obtained worldwide shows that early surgery should be the preferred management approach for organic MR. This approach differs from standard guidelines, and it is essential that its principles, rationales, and conduct be fully considered. Response by Gillam and Schwartz see p 804 Guidelines for the management of valve diseases mention class I versus class II indications as having agreed-on versus conflicting evidence/opinions.5 This classification is problematic for MR treatment because class I indications, based mostly on symptoms and overt left ventricular (LV) dysfunction, lead to the performance of rescue surgery (surgery for patients at considerable risk if unoperated) but do not result in optimal long-term outcomes for patients with organic MR.6,7 The concept of uniform surgical recommendations that supposedly apply equally to all centers is also problematic; recent studies have shown that the quality of …

Ventilatory strategies for patients with acute brain injury

The ventilation of patients with acute brain injuries can present significant challenges. Frequently, guidelines recommending management strategies for patients with traumatic brain injuries come into conflict with what is now considered best ventilatory practice. In this review, we will explore many of these areas of conflict. The use of ventilatory strategies to control partial pressure of carbon dioxide in patients with traumatic brain injury is associated with the development of acute lung injury. Analysis of the International Mission for Prognosis And Clinical Trial (IMPACT) database has confirmed the association between hypoxia and poor neurological outcome. Although a recent meta-analysis has suggested a survival benefit for steroids in acute lung injury, the use of steroids has been associated with a worsening of outcome in patients with traumatic brain injuries and their effects on the brain have not been fully elucidated. There are unlikely to be randomized controlled trials advising how best to ventilate patients with acute brain injuries because of the heterogeneous nature of such injuries. Hypoxia should be avoided. The more widespread use of multimodal brain monitoring, including brain tissue oxygen and cerebral blood flow monitoring, may allow clinicians to tolerate a higher arterial partial pressure of carbon dioxide than has been traditional, allowing a less injurious ventilatory strategy. Modest positive end-expiratory pressure can be used. In severe respiratory failure, most 'rescue' strategies have been attempted in patients with acute brain injuries. Choice of rescue therapy at present is best decided on a case-by-case basis in conjunction with local expertise.

No direct effects of erythropoietin beta on a head and neck squamous cell carcinoma cell line which is growth stimulated in vivo

Introduction. Erythropoiesis-stimulating agents (ESAs) are used in cancer therapy to reverse anaemia. It has been suggested that ESAs might improve treatment outcome by reducing tumour hypoxia, but ESAs might also increase tumour growth. In this work, the effect of recombinant human erythropoietin (rHuEpo) β was investigated on a human head and neck squamous carcinoma cell (HNSCC) line in vitro. The cell line was previously growth stimulated in combination with surgery in a xenograft model and the investigation was initiated to see if rHuEpo directly affects the tumour cell line, alone or in combination with cell stress, or if the in vivo effect should be attributed to secondary effects. Material and methods. The cell line LU-HNSCC-7 was grown in vitro and treated with rHuEpo alone or in combination with radiation, cisplatin, hypoxia or tumour extracts. The expression of the Epo receptor (EpoR) was investigated by western blotting after one- and two-dimensional electrophoresis, RT-PCR and through analysis of the effect on EpoR signalling. Results. The cell line was shown not to express EpoR. Furthermore, it was only possible to detect a minor effect on cell growth (1.4 times over control, p < 0.001) under specific conditions and at supra-pharmacological concentrations of rHuEpo β. No effect was detected on cell migration. None of the cell stressing treatments could enhance the minor growth stimulatory effect of rHuEpo β. Discussion. The conclusion is that rHuEpo β does not stimulate tumour growth of the investigated cell line through a direct interaction with tumour cells. We hypothesise that interactions with stromal cells and the stimulation of wound healing responses might, at least partly, explain the negative effects of ESA administration during cancer treatment. We propose that EpoR expression in HNSCC tumour cells might not be a good marker for prediction of ESA induced worsening of outcomes after cancer treatment.

Facial Nerve Repair

The purpose of this article is to review a large series of patients evaluated for disorders of the facial nerve in order to assess the indications for surgery, the timing of surgery, the techniques of nerve repair, and to better define those factors associated with a favorable outcome. Study design: A retrospective review of patients undergoing facial nerve repair from 1963-1997. Methods: One hundred and three patients underwent surgical intervention designed to repair a disrupted facial nerve. All procedures were performed by one of the senior surgeons (M.M.). Seventy-two patients had a complete data set and at least one year of follow-up. Results: Eighty percent of patients attained an outcome considered superb to fair. Twenty percent of patients had a poor outcome. There was a slight worsening of outcome with increased time to repair. Patients with a neoplastic etiology of nerve paralysis tended to have a worse outcome. Conclusions: Facial nerve grafting is most successful if intervention is undertaken at or near the time of initial injury. However, prolonged time (up to two years) to repair does not preclude the potential for some recovery. The limitations of the current systems for grading facial recovery after nerve repair are well known, and the adoption of a new grading scale for assessing recovery after reanimation procedure is recommended.

Treatment of heart failure with beta-blockers. Mechanisms and results.

Sympathetic activation is a significant predictor of a poor prognosis in heart failure. Excessive stimulation with norepinephrine produces apoptosis, tachycardia and arrhythmias thereby leading to progression of left ventricular dysfunction and worsening of outcome. Beta-blockers reduce morbidity and improve cardiac function. They have been shown to improve survival (MERIT-HF, CIBIS II and US-Carvedilol Trials). A careful uptitration of dosages is achievable with a low rate of side effects. The mechanism of beta-blocker effects in heart failure are cardiac protection from beta1-adrenoceptor overstimulation, antiarrhythmic effects, reduction in heart rate and positive energetic effects or a combination thereof.

Laparoscopic cholecystectomy and cirrhosis:a case-control study of outcomes

The incidence of gallstone disease in patients with cirrhosis is greater than that in healthy patients. Previous surgical literature reported greater morbidity and mortality in patients with cirrhosis with both open and laparoscopic cholecystectomy (LC). We compared our recent experience with LC in patients with cirrhosis and controls. A retrospective review was performed using the search terms, “cirrhosis” and “laparoscopic cholecystectoaiy” Forty-eight patients with cirrhosis were identified and randomly matched with healthy controls by age and sex. Four controls were assigned per patient with cirrhosis. Outcomes assessed included mortality, duration of surgery, length of hospital stay, blood transfusion requirement, postoperative complications, and need for conversion to open cholecystectomy. Forty-eight patients with cirrhosis and 187 healthy controls underwent LC. Child-Pugh classification of severity of liver disease was as follows: Child's class A, 38 of 48 patients; Child's class B, 10 of 48 patients; and Child's class C, 0 of 48 patients. Patients with cirrhosis had statistically significantly lower albumin levels ( P = .0001) and prolonged prothrombin times ( P = .05). Average duration of surgery for patients with cirrhosis was 1.71 versus 1.57 hours ( P = .57) for controls. Average length of hospital stay for patients with cirrhosis was 6.47 versus 4.77 days ( P = .152) for controls. Average number of units of blood transfused in patients with cirrhosis was 0.156 versus 0.0 units ( P = .025) in controls. Complications occurred in 6 of 48 patients with cirrhosis (12.5%) and 8 of 187 controls (4.2%; P < .05). No child's class C patient underwent LC. Four patients with cirrhosis (8.3%) and no controls were converted to open cholecystectomy. No postoperative infections were noted. There was no mortality in either group. LC in patients with Child's class A and B cirrhosis is reasonably safe and shows no increase in morbidity or mortality or worsening of outcome. Further studies are required to evaluate the management of acute gallbladder disease in Child's class C patients.

0.45% saline and 5% dextrose in water, but not 0.9% saline or 5% dextrose in 0.9% saline, worsen brain edema two hours after closed head trauma in rats.

In this study, we examined the effect of four i.v. fluids (250 mL/kg) on blood glucose and osmolality and brain tissue specific gravity after closed head trauma (CHT) in rats. CHT was delivered at Time 0; blood was sampled at 60 min; fluid infusion began at 75 min and ended at 105 min. Blood was again sampled at 105 and 120 min, and brain tissue specific gravity was determined at 120 min. Five groups (one control and four fluid-treated groups) received CHT, and five other groups (one control and four fluid-treated) did not (n = 9 in each group). 0.45% saline (1/2 NS) and 5% dextrose in water (D5W) accentuated the decrease of brain tissue specific gravity (1.0366 +/- 0.0025 and 1.0368 +/- 0.0028, respectively; mean +/- SD) caused by CHT (1.0395 +/- 0.0036), but 5% dextrose in 0.9% saline (D5NS) and 0.9% saline (NS) did not (1.0431 +/- 0.0042 and 1.0389 +/- 0.0049, respectively). In addition, 1/2 NS decreased blood osmolality (248 +/- 6 mOsm/L), D5W increased blood glucose (1095 +/- 173 mg/dL), D5NS increased blood osmolality (350 +/- 5 mOsm/L) and glucose (1695 +/- 76 mg/dL), and NS caused no significant change. We conclude that administering hypoosmolar i.v. fluids after CHT causes a significant worsening of cerebral edema 2 h after CHT. We previously reported worse neurological outcome and/or mortality after closed head trauma in rats when 5% dextrose in water or 0.45% saline was given i.v. compared with 0.9% saline or 5% dextrose in 0.9% saline. The present results and our previous findings indicate that worsening of outcome after closed head trauma in rats may be caused more by edema formation than by hyperglycemia.

Aprotinin Versus Lysine Analogues: The Debate Continues

The decision to use any pharmacologic intervention inevitably rests on balancing the efficacy and safety of the intervention. The advent of the acquired immunodeficiency syndrome epidemic greatly increased awareness of transfusion-related illnesses and focused attention on methods to prevent the need for blood and blood products. This has led, especially in the last decade, to increased use of drugs to help reduce perioperative bleeding. This chapter focuses on the lysine analogues and aprotinin as the serine protease inhibitor currently available in clinical practice. Both groups of compounds have recently shown promise in reducing surgical bleeding. However, the reader will notice that none of these agents are new; they have all been available for more than 30 years. What is new is their use in preventing bleeding. We therefore have considerable knowledge regarding the safety of these compounds. The first part of this review will compare the actions of these two types of agents on the processes related to thrombosis, hemostasis, and fibrinolysis. This is followed by a comparison of the efficacy of each intervention and any dose-response relationship. This section highlights the reported reduction in postoperative bleeding with both classes of agent. There is, however, no obvious or consistent reduction in the transfusion of blood and blood products in patients given lysine analogues. In contrast, there is a consistent reduction in the need for blood transfusions in patients given aprotinin therapy. The next major section will discuss the evidence to suggest that these drugs may, because of their known effects on the processes related to inflammation, hemostasis, and cellular repair, contribute to an improvement or worsening of outcome after cardiac operations. In particular, this section focuses on the antiinflammatory actions and modifications in vascular tone associated with aprotinin therapy. These effects may be related to improved outcome in patients by reducing the incidence of permanent neurologic deficit or stroke after heart operations, as well as inhibiting pulmonary vascular hyperreactivity and hypertension in susceptible individuals. Finally, this brief review discusses the safety issues that have been raised in regard to each of these classes of agents, specifically problems associated with abnormal renal function, hypersensitivity reactions, and thrombotic complications.

The influence of obesity on post-operative complications and operative difficulty in open and laparoscopic cholecystectomy

SummaryThis prospective study explores the relationships between obesity, technical difficulty and outcome in open (OC) and laparoscopic (LC) cholecystectomy. Body mass index (BMI = kg/m2) was used to classify 332 patients undergoing OC (n = 116) or LC (n = 216) as: normal weight (NW) BMI <25, overweight (OW) BMI 25–29.9 and obese (OB) BMI ≥ 30. The operative difficulty of each operation was graded by the surgeon and all complications were recorded. The overall complication rate for all 332 patients was not affected by BMI: NW group 11/147 (7.5%), OW 15/122 (12.3%) and OB 5/63 (7.9%) (NS). Similarly, there was no evidence of worsening of outcome in OB compared with NW and OW patients undergoing laparoscopic or open cholecystectomy. Subjective assessment of operative difficulty revealed that access to the gall bladder was better (Chi-squared = 16.6, P < 0.001), dissection was easier (Chi-squared = 9.7, P < 0.001) and the whole procedure less difficult (Chi-squared = 11.5, P < 0.001) in LC compared with OC....

Recurrent Squamous Cell Carcinoma of the Vulva: A Study of 73 Cases

In a study of 73 patients, diagnosed with recurrent squamous cell carcinoma of the vulva between 1975 and 1990, the effect of clinical variables on the outcome was evaluated. The overall 5-year survival rate was 35.2%. Of the 73 patients, 33 (45.2%) originally had Stage I or II disease and 40 (54.8%) Stage III or IVA; 49 (67.1%) recurred less than 2 years and 24 (32.9%) more than 2 years after initial surgery; and 39 (53.4%) recurred on the vulva only, while 34 (46.6%) recurred beyond the vulva. Of 59 patients who had groin lymph node dissection at initial surgery, 26 (44%) had negative and 33 (56%) had positive nodes. By means of univariate analyses, a significant worsening in outcome was demonstrated with advancing original stage of disease (P < 0.001), positivity of groin lymph nodes (P < 0.01), shortening of recurrence-free interval (P < 0.001), and extension of recurrence beyond the vulva (P < 0.001). In a multivariate analysis (Cox proportional hazards model) recurrence site was the strongest and the only significant predictor of survival. The death risk showed a 3.7-fold increase (95% confidence intervals: 1.6 to 8.7, P = 0.002) for recurrence beyond the vulva over recurrence on the vulva only. For patients who recurred in the vulva only, wide radical local excision provided acceptable survival results, while for all other patients, regardless of type of treatment, the outcome was poor.

Recovery from diffuse traumatic brain injury in Johannesburg: a concurrent prospective study.

Three hundred and twenty-six persons with light, moderate, or severe diffuse traumatic brain injury (TBI) were assessed during initial hospitalization in Johannesburg. One hundred and forty-four were followed up at approximately six months, 83 at 12 months, and 71 at 24 months posttrauma. The sample attrition rate was high. When patients could not be found, data were obtained from their caregivers. Recovery was measured in five different areas of functioning: family relationships, psychologic problems, activities of daily living (ADL), employment status, and physical status. Psychologic problems and family relationships worsened with time, but proficiency in ADL improved; physical and employment status remained relatively stable during the survey period. Severity of injury was significantly correlated with outcome in each functional area at some point in the follow-up period. Discrepancies between patients' and caregivers' perceptions of outcome were noted, particularly in the area of psychologic functioning. Caregivers tended to rate the recovery made by the patient as better than the outcome patients perceived themselves to have made. These differences in perception diminished with time. The multifactorial nature of recovery after TBI is indicated by the improvements seen in some functional areas and the worsening of outcome in other areas. These findings suggest that rehabilitation programs for persons with TBI should (1) include caregivers, (2) focus on the adjustment of both parties to their new circumstances, and (3) facilitate a convergence in their perceptions. Adequately defining recovery is a first step to estimating the prevalence of TBI, but necessitates further work. Epidemiology awaits a better understanding of the recovery process after TBI.

Secondary hypotensive insults in a rat forebrain ischemia model

Previous studies have shown that the recently injured brain has an increased sensitivity to subsequent brief episodes of severe ischemia. This investigation was designed to assess whether less severe secondary insults, which alone would be incapable of producing injury, exacerbate brain damage resulting from a primary episode of global ischemia. Rats were subjected to either 10 min of 2-vessel forebrain ischemia (primary insult alone), 20 min of hypotension (mean arterial pressure, MAP=either40or25mmHg) without vessel occlusion (secondary insult alone), or 10 min ischemia followed 1 h later by the hypotensive challenge (primary+secondary insult). Seven days later, the animals were neurologically evaluated and the brains then prepared for histologic analysis. Neither magnitude of secondary insult alone was found to produce injury. In contrast, the primary insult alone caused moderate damage in the hippocampus, caudoputamen and neocortex. With the exception of increased neuronal necrosis in the hippocampal CA1 sector in rats receiving the primary + secondary insult ( MAP= 25mmHg), no worsening of outcome could be attributed to the secondary insults. These results indicate that the recovering brain may not be as sensitive to hypoperfusion as has previously been suggested.

Cerebral Metabolic Depression and Brain Protection Produced by Midazolam and Etomidate in the Rat

Midazolam and etomidate have been shown to depress cerebral metabolism and may protect the brain during ischemia. However, it has been reported that etomidate may produce EEG spiking activity and seizures, which could adversely affect outcome. We compared the effects of midazolam and etomidate on EEG, cerebral blood flow (CBF), and cerebral cortical oxygen consumption (CMRO2) as well as neurologic outcome following incomplete cerebral ischemia in the rat. CBF was measured with radioactive microspheres and cortical CMRO2 was calculated by multiplying cortical CBF by the arterial-sagittal sinus oxygen content. Incomplete ischemia was produced by unilateral carotid artery occlusion combined with hemorrhagic hypotension. In low doses (0.02 mg/kg/min i.v.), both midazolam and etomidate depressed EEG, decreased CMRO2, and improved outcome from ischemia compared to nitrous oxide control rats. At a higher dose (0.2 mg/kg/min i.v.), midazolam further depressed EEG and CMRO2 and again improved outcome compared to N2O controls. In contrast, high dose etomidate (0.2 mg/kg/min) produced spiking EEG activity without further depression of CMRO2 and a worsening of outcome following cerebral ischemia. These results support previous reports that midazolam and etomidate may protect the brain from incomplete cerebral ischemia but suggest that EEG spiking activity associated with high dose etomidate may be associated with a worse outcome.

Central somatosensory conduction time and acoustic brainstem transmission time in post-traumatic coma.

Short-latency evoked potentials (SEPs) of the scalp and neck after median nerve stimulation and acoustic brainstem evoked potentials (BAEPs) were recorded in 85 patients in post-traumatic coma with clinical signs of brainstem impairment between days 2 and 6 after trauma. The central somatosensory conduction time (CCT), the amplitude ratio (AR) N20:N13, the interpeak latencies (IPL) I-III, III-V, I-V, and the ARs between waves I and V (I:V) and between wave I and the wave IV/V complex (I:IV/V) were calculated and related to the outcome of the patients. In cases of coma due to supratentorial lesions, CCT and ARs of SEPs were close to normal in patients with good outcome: CCT increased and ARs decreased with worsening of outcome. In cases of primary brainstem injury, a significant prolongation of CCT was also seen in patients with good recovery, whereas normal CCTs could be found in patients with severe disability and death outcome. In this case, unilateral absent scalp SEPs were frequently found. The IPLs I-III, III-V, I-V, and the ARs of BAEPs increased with worsening of outcome. Significant differences of IPL I-V and III-V (brainstem transmission time) were seen between patients with good recovery or moderate disability outcome and the patients with severe disability or death outcome. There was no difference in BAEPs between patients with primary brainstem lesion and patients with secondary brainstem lesion. Patients with bilateral absent SEPs and bilateral absent BAEPs not related to traumatic or preexisting hearing disorders died or survived severely disabled. Unilateral absence of scalp SEPs and unilateral absence of BAEPs were frequently found in patients who died or who had severe disability. Asymmetries in scalp SEPs appeared to be distributed equally to all outcome categories, but asymmetries in BAEPs increased with worsening of outcome too. In most of the patients who died or survived disabled, both SEPs and BAEPs were abnormal.

Central somatosensory conduction time and short latency somatosensory evoked potentials in post-traumatic coma

Short latency evoked potentials (SEPs) were elicited by stimulation of the median nerve at the wrist and recorded simultaneously from the neck and the contralateral scalp in 44 comatose patients with signs of brain stem impairment due to head injury. Thirty-four patients were studied in acute coma on day 1 or 2 after brain injury. Twenty-three patients were studied in prolonged coma during days 3–12 after trauma. Six patients were examined in brain death. Brain stem involvement was divided clinically and by CT scan into secondary lesions due to supratentorial mass displacement and primary lesions due to direct violence to the brain stem. The central somatosensory conduction time (CCT) was measured by subtracting the peak latency of the major response from the neck (N14) from that of the primary scalp response (N20). The amplitude ratios (ARs) N20/N14 were calculated for each trace. Further asymmetries and absence of SEP over one or both hemispheres were noted. In cases in coma due to supratentorial lesions CCT and AR were close to normal in patients with good outcome. CCT increased and AR decreased with the worsening of outcome both in acute and prolonged coma. Asymmetries of SEPs indicated moderate or severe final disability. Patients with absent SEPs over one or both hemispheres due to supratentorial lesions died or survived severely disabled (1 case). In patients suffering from primary brain stem dysfunction, confirmed by a normal or slightly abnormal CT scan, prolonged CCT, asymmetric but also absent SEPs were also found in patients with good outcome both in acute and prolonged coma. AR was generally low in these cases. Early appearance of SEPs or early recovery of initially distorted SEPs and decrease of CCT in prolonged coma or during recovery was a favourable prognostic sign. Therefore even absent or severely distorted SEPs should be interpreted cautiously in patients who may suffer from primary brain stem involvement. Scalp SEPs were totally absent in patients with brain death.

Incidence and prognostic value of spindles in post-traumatic coma

One hundred and thirty-three EEGs were analysed from 80 comatose patients with signs of brain stem impairment due to head/brain injury. Seventy EEGs were taken in acute coma on day 1 or 2 after brain injury. Sixty-three EEGs were recorded in prolonged coma 3–12 days after brain injury. Brain stem involvement was divided by neurological signs and by CT scan into secondary lesions due to supratentorial mass displacement and primary lesions due to direct violence to the brain stem. Different EEG patterns were observed, but spindle activity was of special interest. Spindles were classified as typical (easily recognizable, well organized, 12–14 c/sec activity) or atypical (hardly recognizable, distorted form, 6–11 c/sec activity). Furthermore, asymmetries of spindles were noted. The spindles and their alterations were related to different stages of outcome. Spindles were seen in 91% of the EEGs in acute coma and in 30% in prolonged coma. In acute coma due to secondary brain stem involvement a good outcome was heralded by the occurrence of typical symmetrical spindles combined with early stages of secondary brain stem impairment at neurological examination. In cases of primary brain stem involvement typical spindles also suggested a good prognosis despite the observation of serious clinical signs (decerebrate posturing). The percentage of spindle activity decreased, and distortion and asymmetry of spindles increased with the worsening of outcome. Severe intracerebral lesions (confirmed by clinical and CT scan examinations) led to distortion, asymmetry and finally disappearance of spindles. In prolonged coma spindle activity was markedly reduced regardless of the final outcome. When spindles were present atypical and asymmetric forms significantly increased in patients with bad outcome. There were no significant differences in spindle activity in the different outcome categories, if primary and secondary brain stem lesions were compared.