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SUMMARY Early changes in coagulation were found in patients following a paracetamol overdose. Low levels of clotting factors II, V and VII were present within 24 hours of the overdose. As the levels of factor II correlated with plasma fibrinogen values at this time, it is possible that they were consumed in the process of intravascular coagulation, although this was not supported by the presence of raised titres of fibrin degradation products. The prothrombin time ratio was greater than 2-2 within 30 hours of ingestion of the overdose in all patients who eventually died, whereas it was less than this in those developing only moderate liver damage. The administration of fresh frozen plasma to patients did appear to reduce the maximum abnormality of the prothrombin time ratio, which was significantly less three days after the overdose in the group receiving fresh frozen plasma. However, the coagulation disturbance was of short duration, and the prothrombin time ratio had also returned to normal within one week of the overdose in the control patients, and the administration of fresh frozen plasma did not appear to reduce the morbidity or mortality in the treated patients.Paracetamol is frequently taken as an overdose in suicidal attempts, and hepatic damage of all grades of severity, from minor to fulminant hepatic failure, may result (Prescott, Wright, Roscoe, and Brown, 1971). In the latter group bleeding is often a major problem and is not infrequently the direct cause of death. It is thought to be due in part to low levels of clotting factors resulting both from impaired hepatic synthesis and increased consumption from intravascular coagulation (Rake, Flute, Shilkin, Lewis, Winch, and Williams, 1971). To replace this synthetic deficiency we have advocated the regular use offresh frozen plasma (FFP), although controlled evidence of its value was lacking.In this paper we describe detailed studies, including individual clotting factor assays, in 66 patients seen shortly after a paracetamol overdose, together with the results of a controlled trial of FFP in those patients in whom a severe coagulation disturbance subsequently developed.

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Effective emergency preparedness and response requires leadership that can accomplish perceptive coordination and communication amongst diverse agencies and sectors. Nevertheless, operating within their specified scope of authority, preparedness leaders in characteristic bureaucratic fashion often serve to bolster the profile and import of their own organization, thereby creating a silo effect that interferes with effective systemwide planning and response. This article describes a strategy to overcome traditional silo thinking: "meta-leadership," overarching leadership that intentionally connects the purposes and work of different organizations or organizational units. Thinking and operating beyond their immediate scope of authority, meta-leaders provide guidance, direction, and momentum across organizational lines that develop into a shared course of action and a commonality of purpose among people and agencies that are doing what may appear to be very different work. Meta-leaders are able to imaginatively and effectively leverage system assets, information, and capacities, a particularly critical function for organizations with emergency preparedness responsibilities that are constrained by ingrained bureaucratic patterns of behavior.

With this fluorometric method for measuring indocyanine green (ICG) in biological fluids, the limit of detection is an order of magnitude lower than for the traditional spectrophotometric procedure. The excitation and emission maxima are 780 and 810 nm, respectively. Agreement was excellent (r = 0.998) between direct results by this method and those by a liquid-chromatographic procedure with spectrophotometric detection. ICG breaks down in aqueous solution; the degradation products can be detected with liquid-chromatographic/spectrophotometric methods, but because the metabolites are not fluorescent, they do not interfere in the method present here. The increased specificity and sensitivity of this method should permit much more complete analysis of the kinetics of ICG disposition.

Thirty-six patients at the University of Kentucky Medical Center underwent percutaneous endoscopic jejunostomy placement between January 1 and December 31, 1989. We retrospectively reviewed their charts for indications and complications of the procedure. Experience and outcome with the initial placement of the percutaneous jejunostomy tube was evaluated. Primary diagnoses at the time of insertion included central nervous system disorders (28), ventilator dependence (5), cancer (2), and gastroparesis (1). The follow-up period ranged from 2 to 131 days (median 16 days). Tube dysfunction or dislodgment occurred in 31% of patients. Other complications included pulmonary aspiration (11%) and bleeding at the insertion site (3%). The 30-day mortality rate was 19% with all but one death caused by the severity of the underlying primary illness. It is concluded that problems with the currently performed technique of percutaneous endoscopic jejunostomy, along with tube-related problems, seriously limit the usefulness of this technique. Improvements in technology, along with routine postprocedure radiographs to allow early detection of malpositioned jejunostomy tubes, may improve the outcome of this procedure. Newer techniques that have a higher success of distal small intestinal placement need to be evaluated.

SUMMARY Thirty patients with various types of chronic liver disease and a prothrombin time prolonged for four or more seconds who required needle liver biopsy for diagnostic purposes were given either fresh frozen plasma or a concentrate of clotting factors as a prophylactic measure.The prothrombin time returned to within normal limits in seven of the 15 patients given the concentrate and in three of those receiving fresh frozen plasma. Levels of factors II, IX, and X showed increases of about 30% following concentrate administration; corresponding rises in the group given fresh frozen plasma were less. This was because of the smaller quantity of clotting factors administered with fresh frozen plasma and the increase in factor II and IX activity/kg body weight/unit of clotting factor injected was greater when fresh frozen plasma was used. In neither group was there clinical evidence of bleeding, but it was of interest that most of the clotting factor levels, except in factor II, before biopsy were above those normally required for haemostasis.No evidence of disseminated intravascular coagulation was found with the concentrate injection, and the most worrying finding was the appearance of HBAg some months later in three patients, two from the concentrate group and one from those given fresh frozen plasma. However, the conversion of these patients to HBAg positive may be unrelated to the clotting factor replacement therapy.The risk of bleeding with a liver biopsy is considered to increase if the prothrombin time is prolonged more than three seconds (Sherlock, 1968). There are, however, some patients with prolonged prothrombin times in whom this investigation is needed for diagnostic purposes. Prophylactic administration of clotting factors would be expected to reduce the risks of bleeding in these patients, and for some years it has been our practice to infuse fresh frozen plasma immediately before liver biopsy. With the development of a concentrate of clotting factors which can be given as a single intravenous injection, the necessity for an indwelling intravenous catheter and the administration of the water and sodium load present in fresh frozen plasma could be avoided. Such concentrates contain a high concentration of clotting factors II, IX and X, the levels of which are all reduced in liver disease (Roberts and Cederbaum, 1972), and in this paper we describe a comparison with fresh frozen plasma in the correction of the coagulation defect in patients with a prolong-

SUMMARY Levels of clotting factors II, V, and VII were measured on admission and then daily in 12 patients with grade IV hepatic coma due to fulminant hepatic failure. Factor VII levels obtained within 36 hours of the development of grade IV coma were not of value in predicting which patients would subsequently recover consciousness. Four of the latter group had levels below 9 Y. at this time while the levels in three of the seven fatal cases were higher. Serial determinations were of more value and levels rose rapidly in those patients who ultimately made a complete recovery.The mortality in fulminant hepatic failure is closely related to the degree of encephalopathy which develops and is over 80% in those who deteriorate to deep coma-that is, grade IV encephalopathy- (Trey and Davidson, 1970). Within this fatal group there may well be cases with such extensive hepatic necrosis that recovery of the liver is impossible and the only conceivable treatment is liver transplantation. In others, recovery is a possibility provided that they can be brought through the acute phase of the illness by some means of temporary liver support. If these two groups of patients could be differentiated at an early stage, then this would clearly be of help in considering their possible management.Raised levels of oc foetoprotein indicate a good prognosis but these are found only later in the course of the illness (Karvountzis and Redeker, 1974). The galactose elimination test also appears to be of some value as a prognostic test but is relatively difficult to perform (Tygstrup et al., 1975). Recently, Dymock et al. (1975) have suggested that reductions in levels of clotting factor VII to less than 9% of normal carry a very poor prognosis. However, these results were obtained in a series of patients with hepatic encephalopathy of varying severity ranging from slight to severe, and it is well known that the prognosis is very much better in patients in whom the encephalopathy is relatively mild. The purpose of the present study therefore was to determine whether the measurement of factor VII levels would also be of value in patients with grade IV hepatic coma, in whom the problem of prediction is much more difficult.