Correlation between urine ketones (acetoacetate) and capillary blood ketones (3-beta-hydroxybutyrate) in hyperglycaemic patients.

AIMS: To facilitate the transition from urine ketones (acetoacetate) to capillary blood ketones (3-beta-hydroxybutyrate), we studied the correlation between these two tests. METHODS: Retrospective study of all patients with blood glucose greater than or equal to 2.5 g/l on arrival in the Emergency Department. We studied the correlation between urine ketones (Clinitek 50, Bayer) and capillary blood ketones (Optium, Abbott). We then compared the relative risks (RR) of ketoacidosis and hospitalization associated with each of these tests. RESULTS: In 33 months, 529 adult patients with both urine and blood testing for ketones were enrolled (ketoacidosis 8%, admission rate 49%). Urine ketones scored as +, ++ and +++ corresponded to median capillary blood ketone levels of 0.5 mmol/l (IQR: 0.1-0.9), 0.7 mmol/l (IQR: 0.2-1.8) and 3 mmol/l (IQR: 1.4-5.2), respectively. RRs of ketoacidosis or hospitalization associated with blood ketones greater than or equal to 3 mmol/l were higher than those associated with +++ urine ketones: 74 (95% confidence interval [CI]: 48-88) and 2.9 (95% CI: 2.5-3) versus 31 (95% CI: 18-45) and 2 (95% CI: 1.7-2.1), respectively. CONCLUSIONS: In hyperglycaemic patients in the Emergency Department, a good correlation was observed between urine ketones and capillary blood ketones for low values, but a poor correlation was observed for high values. Either test can therefore be used to exclude ketosis, but the capillary blood ketones test is more accurate to confirm ketoacidosis.

Advantages to using capillary blood beta-hydroxybutyrate determination for the detection and treatment of diabetic ketosis.

Ketone body determination is indicated in all diabetic patients when the risk of ketotic decompensation exists. New methods of screening for ketosis, in particular capillary blood ketone body determination, provide analytical, technical and clinical advantages compared to the conventional ketonuria. It is proposed that a diabetic patient with hyperglycaemia (capillary blood glucose > 2.50 g.l(-1)) and capillary blood ketone bodies exceeding 0.5 mmol.l(-1) requires therapeutic management. For values greater than 3 mmol.l(-1) or in case of more serious clinical symptoms, hospitalisation is indicated, considering the high probability of ketoacidotic decompensation. The advantages of capillary blood ketone body determination including easy use, and rapid and objective results may improve management of the diabetic patient, especially in emergency situations. However, prescription by a physician of capillary blood ketone body determination should be offered to targeted populations that have a high risk of ketoacidotic decompensation, after providing education to patients that is above all aimed at preventing this metabolic complication. In this context of determining ketone bodies in capillary blood, the term "capillary blood ketone bodies" is therefore preferable to the term "capillary blood beta-hydroxybutyrate determination". Indeed, it appears more appropriate, simple, descriptive and significant both for health-care staff and for patients.

Is capillary ketone determination useful in clinical practice? In which circumstances?

A new method is now available to measure capillary levels of 3-hydroxybutyrate (3HB), one of the three ketone bodies. It is a quantitative and enzymatic test that uses the same equipment as for home capillary blood glucose determination but with specific strips. In comparison to urine ketone test, there is no false negative or false positive results, it is highly correlate to standard automate assays and patients find it more acceptable. Clinical implementations of this new test begin to be reported. Some studies showed an advantage of ketonemia versus ketonuria measurement to detect and to treat diabetic ketoacidosis in the emergency room. In diabetic patients treated with continuous subcutaneous insulin infusion, ketonemia seems to be more relevant to detect lack of insulin. In the current care of patient with type 1 diabetes and especially in children blood ketone test is more effective than urine ketone test to prevent hospitalisation during sick days. For other situations such as diabetic pregnancy or type 2 diabetes, more data are needed to determine if capillary measurement of 3HB is really useful. This new test is easier and less unpleasant than doing urinary test but it is still far more expensive. Further clinical studies are needed to define whether self 3HB monitoring should substitute urinary test in outpatient care.

[Acute dyspnea in the emergency room: the utility of troponin, natriuretic, procalcitonin and D-dimers]. / Dyspnée aiguë aux urgences: utilité des troponines, des peptides natriurétiques, de la procalcitonine et des D-dimères.

In emergency, some "low cost" biological tests are too often systematically performed while others are not prescribed because they are considered "too expensive". Good practices for biological testing are in fact the real means for saving money. Here, in order to help for defining those good practices, we review emergency medical approach and, as an example, specify findings concerning the clinical utility of key blood analyses in patients with acute dyspnea. Emergency laboratory testing is usefull when it contributes to establish the diagnosis or to evaluate comorbidity or to stratify disease severity. In a given emergency context, clinical utility must be anticipated according to a bayesian approach with an estimation of the post-test probabilities using the likelihood ratios (estimated from literature) and the pretest probabilities (established by examination at the bedside). The likelihood ratio is the best criterion for diagnostic accuracy of a biological test. According to this criterion, troponin, natriuretic peptides, procalcitonin and D-dimers are four "costly" markers but which can significantly contribute to the etiologic diagnosis of an acute dyspnea. Troponin, natriuretic peptides and procalcitonin are also prognostic markers and are valuable parameters for stratifying disease severity according to their initial value and their plasmatic kinetic during the clinical course of the disease. In conclusion, it is not only the cost of the test but overall the potential impact of its result on the management of the patient's care which makes the decision of performing the test or not.

[Secrecy in children with HIV infection]. / Le secret chez les enfants infectés par le VIH.

The secrecy surrounding the disease of parents and children infected with HIV leads to psychic and affective isolation and difficulties of communication within the family. Psychological management may possibly help to resolve the problem of secrecy between parents and children. We analyzed the organization and dynamics of the secret surrounding children contaminated by their mothers. The analysis was prospective and was based on semi-directive interviews and drawings. We followed up, over a period of two years, ten children (mean age: 4 years, range: 4 months to 12 years) with different ethnic and socio economic backgrounds. In each family, the child was the target of the secret, the pediatrician the guardian, and the mother (or her substitute) the keeper. The organization of the secret around the other potential guardians varied from one family to another. Two modes of intra-family communication were observed: the secret (reserved for the youngest children) and the tacit. One child suffered from a disorder related to the secret, the others had depressive and reactional symptoms. At the end of the study, the manner of approaching, and especially dealing with, the question of the secret had changed appreciably in each family: disclosure to the family circle (three cases), passage of the child from the secret to the tacit (two cases), and easier questioning of the pediatrician in all of the cases. Nonetheless, in no case had the secret been completely lifted for the child. Four children asked to continue psychological management. The changes in the dynamics of the secret and the appeasement observed in the families suggest that psychotherapeutic aid should be offered to families where a child has been contaminated with HIV by the mother.

[Acute poisoning by beta-blockers and by calcium inhibitors]. / Intoxications aiguës par les beta-bloquants et par les inhibiteurs calciques.

beta-blockers and calcium-channel inhibitors are frequently used for self-poisoning. Propranolol and verapamil, the leading drugs in each pharmacological class, are the most toxic. They interfere with intracellular calcium concentration in muscles. Circulatory insufficiency may be due to vasodilatation, myocardial depression or severe bradycardia. If one respects a specific sequence for administration, the usual antidotes (glucagon, calcium salts, isoprenaline, epinephrine) are usually efficient. One must not underestimate the risk of worsening of an intoxication that is seen at the early stage, that occur in an old person or in a patient with heart disease, or that depress ventilation. Hence, it is important to monitor and treat these intoxications in an intensive care unit.

Treatment of acute chloroquine poisoning: a 5-year experience.

OBJECTIVE: To describe various aspects of prognostic and therapeutic importance in patients treated for acute chloroquine poisoning. DESIGN: Retrospective study. SETTING: Toxicology intensive care unit (ICU) of a university hospital. INTERVENTIONS: None. PATIENTS: One hundred sixty-seven consecutive patients with acute chloroquine overdose admitted to our toxicology ICU. MEASUREMENTS AND MAIN RESULTS: The mean amount ingested by history was 4.5 +2- 2.8 g. and 43 (26%) of 167 patients ingested > 5 g. The mean blood chloroquine concentration on admission was 20.5 +/- 13.4 mumol/L The majority (87%) of our patients received at least one arm of a combination therapy regimen (epinephrine, mechanical ventilation, diazepam). cardiac arrest occurred in 25 patients before hospital arrival; In seven of these patients, cardiac arrest occurred immediately after injection of thiopental. The mortality rate was 8.4% overall, and was 9.3% in patients with massive ingestions (NS vs. the group as a whole). We did not find a meaningful correlation between the amount ingested as estimated by history and the peak blood chloroquine concentration; the latter was highly correlated with the mortality rate. CONCLUSIONS: The mortality rate in patients with acute chloroquine poisoning, including those patients sick enough to be referred to a specialty unit such as ours, can be limited to < or = 10%. This finding appears to be true even in patients with massive ingestions. We were not able to correlate mortality with amount ingested by history, although the mortality rate does correlate with blood chloroquine concentration. While early use of diazepam, epinephrine, and mechanical ventilation in most of our patients may have contributed to the excellent overall results, these elements, either singly or in combination, do not appear to have a truly antidotal effect in acute chloroquine poisoning. Thiopental, on the other hand, should be used with great caution, if at all, in such cases.

Empiric use of flumazenil in comatose patients: limited applicability of criteria to define low risk.

STUDY OBJECTIVE: To develop clinical rules for the safe and effective use of flumazenil in suspected benzodiazepine overdose. METHODS: We assembled a retrospective series of 35 consecutive comatose patients admitted between October 1992 and July 1993 to a toxicologic ICU with the presumptive diagnosis of drug overdose. These patients were divided into two groups. Group A (low-risk) patients had a clinical picture compatible with uncomplicated benzodiazepine intoxication (calm, without abnormalities in pulse or blood pressure, lateralizing signs, hypertonia, hyperreflexia, or myoclonus) in the absence of predefined electrocardiographic or clinical signs of tricyclic antidepressant or other proconvulsant overdose, and absence of an available history of long-term benzodiazepine treatment or an underlying seizure disorder. Group B ("non-low risk") comprised all other patients. Efficacy of flumazenil was categorized as complete awakening (with normal level of alertness), partial awakening, or no change in alertness level. The safety of flumazenil was defined on the basis of the absence of seizures or death. RESULTS: In group A (n=4), flumazenil was associated with complete awakening in three patients and partial awakening in one. No seizures were observed. In group B (n=31), flumazenil was associated with complete awakening in 4 patients, partial awakening in 5, and no response in 22. In group B, five seizures occurred. CONCLUSION: Comatose patients with clinical or ECG criteria thought to contraindicate the use of flumazenil have a reasonably high risk of seizures after administration of this drug. Low-risk patients may be able to receive flumazenil safely, but they may be only a small portion of comatose patients with suspected overdose.

A case of life-threatening lactic acidosis after smoke inhalation - interference between beta-adrenergic agents and ethanol?

A 49-year-old male developed bronchospasm and severe lactic acidosis after exposition to fire smoke. The correction of lactic acidosis following beta-adrenergic agents withdrawal, and the transitory increase in lactate after salbutamol reintroduction are consistent with hypersensitivity to salbutamol. However, the plasma lactate concentration (32.6 mmol/l) that we observed 9.5 h after admission is far above those currently seen after administration of beta-adrenergic agents. We searched for causes able to potentiate the adverse effects of these drugs and we noticed that our patient had a high plasma ethanol level (2.4 g/l). Alcohol metabolism in the liver results in generation of high NADH/NAD+ ratios, thus reducing lactate liver clearance. This observation suggests that plasma lactate levels should be monitored closely in alcoholic patients treated with beta-mimetic agents.

Cardiovascular repercussions of seizures during cyclic antidepressant poisoning.

Cyclic antidepressant overdose involves a risk of generalized seizures and cardiovascular disturbances. We have conducted a retrospective study to test the hypothesis of a relationship between generalized seizures and the onset of arrhythmia, hypotension or cardiac arrest during cyclic antidepressant intoxication. Patients who had seizures after ingestion of toxic amounts of tri- or tetracyclic antidepressants were included. Limb-lead QRS complex duration and systolic blood pressure were recorded before and after seizure. Twenty-four of the 388 patients (6.2%) who were admitted to our ICU over a four-year period had seizures (2.3 +/- 2 seizures/patient). Cardiac repercussions of cyclic-induced seizure were frequent and severe. In the postictal period, broadening of the QRS duration or hypotension occurred or were exacerbated in at least 41% and 29% of cases, respectively. In three patients (12.5%), the seizure-induced cardiovascular state was life-threatening and required massive alkalinization therapy and vasopressors, and two of the three required cardiac massage or cardioversion. Prior to seizure, these three patients had severe intoxications characterized by QRS duration > or = 120 ms and systolic blood pressure < or = 80 mm Hg. The results of this work confirm the potential risk of cardiovascular deterioration after cyclic antidepressant-induced seizure and raise the question of a prophylactic approach especially towards the subgroup with unstable hemodynamic status.

[Shock caused by poisoning. Use of cardiotropic agents]. / Collapsus par intoxication. Utilisation des agents cardiotropes.

At toxic doses, cardiotropic drugs may compromise cardiac output leading to circulatory shock. Specific treatment varies depending on the nature and the dose of the drugs ingested as well as causal mechanism including vasopegia, hypovolaemia, cardiogenic effects and sepsis. Progress in our understanding of the pharmacodynamic aspects of intoxication and the development of specific antidotes has led to reduced morbidity and mortality. In addition to the classical inotropes, mainly catecholamines and phosphodiesterase inhibitors, other therapeutic agents may have specific inotrope effects in such ad hoc situations. These include hypertonic alkaline saline solution, calcium, glucagon, hydroxocobalamine and other cobalt salts, oxygen and immunotoxicotherapy. Together with volum replacement, dobutamine at the dose of 7 to 20 micrograms/kg/min can usually restore cardiac performance in cases of carbamate-induced circulatory shock. In case of tricyclic antidepressant overdose, treatment should include respiratory assistance and infusion of alkaline sodium solutions to both reverse the extracellular acidosis and correct sodium balance. Catecholamines may be necessary in cases with severe hypotension. Major vasoplegia and impaired intraventricular conduction may be induced by overdoses of chloroquine and class I antiarrhythmic drugs. Signs of gravity are: ingested dose above 4 g, QRS > or = 0.12 s or systolic arterial pressure < or = 80 mmHg. Treatment with epinephrine, respiratory assistance and diazepam has been proven effective during the acute phase, but right catheterism is often required due to major haemodynamic instability during the first 72 first hours. Beta-blockers have both a bronchoconstrictor and respiratory depressor effects favouring cardiovascular failure by hypoemia. Symptoms occur in 30-40% of the cases of overdose. Shock results from the reduction in blood pressure and cardiac inotropism. Glucagon, isoprenaline and epinephrine, prescribed in that order, can considerably reduce mortality to less than 4%. Despite the development of specific molecules, the risk of mortality due to toxic shock caused by antiarrhythmics, chloroquine, colchicine, calcium inhibitors and paraquat remains high.

Acute fluvoxamine poisoning.

A total of 221 cases of deliberate acute overdose with fluvoxamine reported to the Paris Poison Centre, and 78 cases collected by the International Drug Safety Department of Duphar BV were analysed. Other agents, mainly benzodiazepines, neuroleptics, other antidepressants and alcohol, were also taken in 77% of the cases. The acute toxicity that could be attributed to fluvoxamine alone was rarely severe. The symptoms observed were always benign when the dose of fluvoxamine was below 1000 mg and included drowsiness, tremor, nausea, vomiting, abdominal pain, bradycardia and/or anticholinergic effects (dry mouth, mydriasis, sinus tachycardia, urinary retention). Seizures occurred in a few cases after high doses (generally > 1500 mg). Cardiotoxicity was not a serious problem; sinus bradycardia was noted with doses of less than 1000 mg, but was always moderate and required no treatment. Conduction abnormalities were rare.

Clinical features and management of digitalis poisoning--rationale for immunotherapy.

The intensity of gastrointestinal and visual symptoms together with hyperkalemia and the characteristic ECG features make diagnosis of acute digitalis intoxication relatively easy. Death results mainly from ventricular fibrillation or from ventricular asystole or pump failure. Mesenteric infarct may also occur in elderly patients. Previous assessment of outcome has shown that mortality increases in patients exhibiting five prognostic factors: 1) advanced age; 2) heart disease; 3) male sex; 4) high-degree atrioventricular block; 5) hyperkalemia. Conventional treatment includes gastric lavage, activated charcoal and supportive care. First-line antiarrhythmic therapy is usually atropine, because of bradycardia-induced arrhythmia. Ventricular pacing is a toxicodynamic treatment that may be helpful in both bradycardia-induced arrhythmia and high-degree atrioventricular block. Pacing is difficult to handle and can result in serious adverse effects. Immunotherapy has two advantages. First, a strong toxicodynamic effect due to quick reversal of digitalis-induced dysrhythmias, hyperkalemia, and myocardial depression, by reactivation of membrane ATPases. Second, a toxicokinetic effect due to accelerated renal excretion of Fab-digitalis complexes. Since this therapy is well tolerated and efficient, we recommend early administration of Fab fragments as soon as poor prognostic factors are identified.

Acute digitalis intoxication--is pacing still appropriate?

Over a six year period, 92 patients intoxicated with either digitoxin or digoxin were admitted to our ICU. Fifty-one patients were treated with cardiac pacing and/or Fab fragments, and the mortality rate was 13% (14 were intoxications with digoxin, 36 with digitoxin, 1 was mixed). Forty-five cases were suicide attempts; six were accidental overdosages. Since cardiac pacing may trigger fatal arrhythmia or delay the administration of Fab fragments, we conducted a retrospective study to determine whether fatal outcomes could be related either to cardiac pacing or to unsatisfactory use of immunotherapy. In our study, prevention of life-threatening arrhythmia failed in 8% of cases with Fab and in 23% with pacing. Though Fab tended to be more effective, this difference was not significant. In our study, the main obstacles to the success of Fab were pacing-induced arrhythmias and delayed or insufficient administration of Fab. Iatrogenic accidents of cardiac pacing were frequent (14/39, 36%) and often fatal (5/39, 13%). In contrast, immunotherapy was not associated with any serious adverse effects (0/28, 0%) and was safer than cardiac pacing (p < 0.05). In conclusion, during digitalis intoxication, the pacemaker has limited preventive and curative effects, is difficult to handle, and exposes patients to severe iatrogenic accidents. Fab fragments act as a powerful antidote and are safer and much easier to use than pacing. These results encourage us to prescribe Fab fragments as first-line therapy during acute digitalis intoxication.