Splenic abscess with Clostridium novyi bacteraemia and sepsis.

Splenic abscess is an uncommon entity and usually results in the death of the patient when left undiagnosed. A case is presented where bacteraemia with an anaerobic Gram-positive bacillus was associated with splenic abscess. Despite treatment with splenectomy and antibiotics the patient developed a multiple organ dysfunction syndrome (MODS) and died. Of particular interest was the isolation of Clostridium novyi type A from the blood in a patient without gas gangrene but with splenic suppuration.

Influence of cardiopulmonary resuscitation on plasma concentrations of nimodipine in the dog.

The influence of cardiopulmonary resuscitation on the plasma concentrations of nimodipine in the anaesthetized dog has been examined. Nimodipine was given as a bolus injection followed by a maintenance infusion. When, during the maintenance infusion, the dogs were subjected to cardiac arrest followed by external cardiac massage combined with artificial ventilation (basic life support), a fast and almost threefold increase in the steady-state plasma concentrations of nimodipine was observed. When the maintenance infusion of nimodipine was stopped immediately before cardiac arrest and basic life support, the nimodipine concentrations decreased. These results indicate that during basic life support, there is a decreased transfer of infused nimodipine from plasma to the tissues. This is also supported by the fact that for antipyrine, a drug with a smaller volume of distribution than nimodipine, the increase in plasma concentrations when infused during cardiac arrest and basic life support, was much smaller. When nimodipine was started after restoration of the spontaneous circulation (advanced life support) in dogs that had been subjected to cardiac arrest and basic life support, the plasma concentrations were not significantly higher than in control dogs. It can be concluded that the fate of nimodipine is markedly altered during basic life support but not in the period following restoration of spontaneous circulation.

Combined intoxication with a tricyclic antidepressive agent and a neuroleptic.

We report the case of a patient who co-ingested a tricyclic antidepressant (2500 mg of doxepin) and a neuroleptic drug (3500 mg of prothipendyl). Following overdose either agent can affect the central nervous and cardiovascular systems, inducing arrhythmias, conduction disturbances and hypotension. The presented case illustrates that a combined overdose of tricyclic antidepressants and neuroleptics enhances the possible toxic effects of each drug and especially the risk for adverse cardiac events. The clinical features and management of this combined intoxication are discussed. Treatment with sodium bicarbonate readily corrected a potentially life-threatening cardiac arrhythmia and is therefore suggested to be imperative in the treatment of these cases.

Reversible cardiac failure in an adolescent after prolonged exposure to carbon monoxide.

We describe the case of an adolescent who developed a severe but fully reversible cardiac dysfunction with low blood levels of carboxy haemoglobin (COHb = 10%) after a prolonged exposure to carbon monoxide. A 15-year-old male was admitted with a Glasgow Coma Scale of 8/15 with suspected postictal state and postanoxic encephalopathy. The cardiorespiratory failure which he developed soon after admission mandated mechanical ventilation, inotropic support and ultimately left ventricular support by intra-aortic balloon counterpulsation. The cardiac dysfunction was documented by radionuclide imaging and echocardiography. The patient fully recovered without neurological deficit. A low blood COHb concentration is a poor safety indicator since high tissue levels of accumulated carbon monoxide can be associated with coma and fulminant cardiorespiratory failure requiring advanced life support facilities.

A prospective, open, single blind, randomized study comparing four analgesics in the treatment of peripheral injury in the emergency department.

The efficacy of four analgesics, distinct concerning analgesic power and mechanism of action, was evaluated for pain relief in patients suffering from single peripheral injury. Patients were randomly allocated to receive either propacetamol (the pro-drug of paracetamol) 20 mg/kg i.v., piritramide 0.25 mg/kg i.m., tramadol 1 mg/kg i.v. or diclofenac 1 mg/kg i.v. Pain scores were measured by the patient using the visual analogue scale (VAS) and by an observer using a 4-point verbal rating scale (VRS). Cardiorespiratory variables and side effects were recorded. One hundred and sixty patients were included, 131 completed the study. Groups matched for demography and baseline pain levels. In general pain scores decreased with time. No significant differences were found between groups at any particular time point. VAS scores were significantly (p < 0.02) lower than baseline scores 30 minutes after injection in all treatment groups except for the piritramide group where significance (p < 0.01) was reached after 60 minutes. VRS score analysis showed a similar trend although significances differed. In the piritramide group significantly more side effects were noted than in the other groups (p < 0.05). We conclude that intravenous propacetamol, tramadol and diclofenac are equally efficacious for emergency analgesic treatment of single peripheral trauma.

Bedside evaluation of intraocular pressure in critically ill patients, ventilated at different levels of positive end-expiratory pressure.

Animal experiments suggest that the application of positive end-expiratory pressure (PEEP) levels > or = 10 cm H2O increase intraocular pressure (IOP), probably through ophthalmic and episcleral venous outflow obstruction secondary to PEEP-induced increase in central venous pressure (CVP). To evaluate whether a similar response occurs in humans, we studied the effects of varying levels of PEEP on IOP in 11 critically ill sedated and mechanically ventilated patients, aged 35 to 88 yrs (mean: 68 yrs), without evidence of ocular disease. Measured variables included PaCO2, PaO2, mean arterial pressure (MAP), CVP and IOP, and were recorded at zero end-expiratory pressure and at 5, 10 and 15 cm H2O PEEP, applied in random order. IOP was measured by the same investigator at the bedside, using a portable and battery-operated tonometer (Tono-Pen). As expected, PaO2 increased significantly from baseline at all PEEP levels. At the three levels of PEEP, no significant change of PaCO2 from its corresponding baseline values was observed. At 5 cm H2O PEEP neither CVP nor IOP raised significantly from baseline. IOP increased significantly (p < 0.01) from 12 +/- 4 to 14 +/- 4 mmHg at 10 cm H2O PEEP and from 13 +/- 4 to 16 +/- 5 mmHg at 15 cm H2O PEEP. CVP also increased significantly (p < 0.01) and in parallel with IOP at 10 and 15 cm H2O PEEP. Since IOP tends to rise significantly when PEEP levels exceed 10 cm H2O, PEEP-ventilated patients in whom such increase is undesirable might benefit from regular bedside IOP monitoring.

Diagnostic markers of sepsis in the emergency department.

Sepsis is defined as the systemic inflammatory response to infection. However, changes in body temperature, heart and respiratory rate and white cell count (the "SIRS" criteria) are not specific enough to identify infected patients in the emergency department. Among many biological parameters, measurement of lactate, central venous oxygen saturation (ScvO2), C-reactive protein (CRP) and procalcitonin (PCT) are of particular interest. Early (within 6h) and goal-directed (ScvO2 > 70%) resuscitation increases survival in severe sepsis and septic shock, particularly in patients with high lactate clearances. CRP and PCT are both useful markers of sepsis but PCT increases earlier, better differentiates infective from non-infective causes of inflammation, more closely correlates with sepsis severity in terms of shock and organ dysfunction and better predicts outcome when followed in time. However, PCT measurement is more costly, time-consuming, and not widespread available. New markers for rapid diagnosis of sepsis (e.g. TREM-1) are under investigation.

Passive immunotherapy of gram-negative bacteremia, sepsis and septic shock.

Despite the use of increasingly potent antibiotics and aggressive cardiovascular monitoring and support, Gram-negative bacteremia and ensuing sepsis and septic shock remain a leading cause of morbidity and mortality after surgery and in critically ill patients. In previous years several new agents and techniques have been developed to improve management and outcome of severe Gram-negative infections. A recently introduced treatment is passive immunotherapy by administration of poly- or monoclonal anti-endotoxin antibodies. The current view--sustained by experimental and human studies--on the mechanism of protection afforded by immunotherapy is that the harmful effects of endotoxin are neutralized by cross-reactive antibodies to the core glycolipid structure of rough mutant Gram-negative bacilli. Two recent large clinical trials reported impressive results achieved through the use of monoclonal anti-endotoxin antibodies in certain subgroups of patients with Gram-negative sepsis. However, this treatment is empirical, expensive and it does not affect overall sepsis mortality. Cytokines such as tumor necrosis factor alpha and interleukin-1 play a pivotal role in sepsis. Experimental studies suggest that specific antagonism of these mediators might offer great perspectives for the treatment of Gram-negative sepsis. An early multi-pharmacological approach aimed at interruption of multiple steps underlying the inflammatory septic cascade will probably constitute the most promising future treatment of severe Gram-negative infectious disease.

Gastric emptying in critically ill patients is accelerated by adding cisapride to a standard enteral feeding protocol: results of a prospective, randomized, controlled trial.

OBJECTIVE: To investigate the effect of cisapride, a relatively new prokinetic agent, on gastric emptying in critically ill patients. DESIGN: Prospective, randomized, controlled study. SETTING: Adult medical/surgical intensive care unit in a university hospital. PATIENTS: Twenty-one consecutively enrolled patients, requiring prolonged mechanical ventilation and enteral feeding. INTERVENTIONS: Patients were randomized to receive either no cisapride or 10 mg of cisapride four times daily, which was added to a standard enteral nutrition feeding protocol. MEASUREMENTS AND MAIN RESULTS: Gastric emptying was evaluated by daily measurements of gastric residue and on days 5 through 7 by bedside scintigraphy. Normal values for gastric clearance of a tracer-labeled test meal and for measurements obtained in the supine position were determined in ten healthy volunteers. The mean time at which 50% of the technetium 99m-labeled test meal was eliminated from the stomach (T 1/2) in this control group was 31 +/- 15 mins. In ten critically ill patients (enteral nutrition group), gastric emptying was markedly delayed after 5 to 7 days of enteral feeding (mean T 1/2 = 78 +/- 40 mins; p < .002 as compared with the control group). In contrast, patients treated with cisapride (cisapride group) showed an accelerated gastric emptying (mean T 1/2 = 18 +/- 7 mins; p > .05 as compared with controls; p < .005 as compared with enteral nutrition group). The mean gastric residue over a 1-wk period was also significantly lower in the cisapride group than in the enteral nutrition group (17.7 +/- 8.9 vs. 94.5 +/- 33.4 mL; p < .001). CONCLUSIONS: The data indicate that gastric emptying in critically ill, sedated, and mechanically ventilated patients can be significantly improved by adding cisapride to a routine enteral feeding protocol.

Plasma concentrations and haemodynamic effects of nimodipine in patients resuscitated after cardiac arrest.

As the pharmacokinetics of a drug may be altered in haemodynamically compromised patients, the plasma concentrations and haemodynamic effects of the calcium entry blocker nimodipine have been examined in patients resuscitated after out-of-hospital cardiac arrest. In 7 patients nimodipine was infused at increasing rates up to 30 micrograms.kg-1.h-1. The plasma concentrations increased with increasing dose; at the highest dose a mean steady-state plasma concentration of 22.1 ng.ml-1 was obtained, and the mean plasma clearance was 1.41.kg-1.h-1. There were no marked changes in mean arterial blood pressure or heart rate. In 9 other patients nimodipine was given as a bolus infusion of 10 micrograms.kg-1 over 3 min, followed by a continuous infusion of 30 micrograms.kg-1.h-1. A mean steady-state plasma concentration of 17.6 ng.ml-1 was obtained and the mean plasma clearance was 1.91.kg-1.h-1. Heart rate did not change significantly, but the mean arterial blood pressure fell. The data indicate that in patients resuscitated after cardiac arrest, the pharmacokinetics of nimodipine are not markedly different from patients with other conditions, e.g. subarachnoid haemorrhage. However, if a loading dose is given to obtain a steady-state concentration sooner, there will be a fall in arterial blood pressure.

Plasma norepinephrine concentrations during resuscitation in the dog.

The objective of this study was to evaluate whether the adrenal glands contribute to the increase in plasma norepinephrine concentrations during cardiopulmonary resuscitation, by releasing norepinephrine and/or by secreting epinephrine that facilitates the release of norepinephrine from sympathetic nerve endings via stimulation of presynaptic beta receptors. The experiments were performed in adrenalectomized and in sham-operated dogs. In adrenalectomized dogs the increase in plasma norepinephrine concentrations during cardiopulmonary arrest and basic life support (BLS) was markedly smaller than in sham-operated dogs. Intravenous infusion of physiologic doses of epinephrine during BLS in adrenalectomized animals did not influence the plasma norepinephrine concentrations. These data indicate that, as suggested by others, the marked increase in plasma norepinephrine concentrations during BLS in dogs is mainly of adrenomedullary origin. They also suggest that presynaptic facilitation of norepinephrine release by epinephrine is not important, but further experiments using higher doses of epinephrine are necessary.

Plasma concentrations of epinephrine during CPR in the dog.

STUDY OBJECTIVE: The purpose of this study was to evaluate whether the marked increase in the plasma concentrations of epinephrine during cardiopulmonary arrest and basic life support (BLS) could be due in part to decreased distribution and/or elimination. DESIGN AND INTERVENTIONS: Dogs were randomly assigned to undergo adrenalectomy or sham-operation. Some adrenalectomized animals received an epinephrine infusion. MEASUREMENTS AND MAIN RESULTS: In the seven sham-operated dogs, the plasma epinephrine concentrations increased markedly during BLS as expected. In the seven adrenalectomized dogs receiving a constant infusion of epinephrine, cardiopulmonary arrest and BLS induced a three to sixfold increase in plasma epinephrine concentrations, with an increase in the mean plasma epinephrine concentrations (calculated from the area under the curve) of 1.21 +/- 0.12 ng/mL (P less than .05). In the seven adrenalectomized dogs receiving a constant epinephrine infusion but not subjected to cardiopulmonary arrest, the plasma epinephrine concentrations remained stable. Finally, in the seven adrenalectomized dogs not receiving an epinephrine infusion, the mean plasma epinephrine concentrations during BLS (calculated from the area under the curve) increased only by 0.05 +/- 0.04 ng/mL, significantly less than in adrenalectomized dogs receiving an epinephrine infusion (P less than .01). CONCLUSION: The increase in plasma epinephrine concentrations during cardiopulmonary arrest and BLS is due in part to an altered disposition of epinephrine.

Cardiac troponins I and T are biological markers of left ventricular dysfunction in septic shock.

BACKGROUND: Cardiac depression in severe sepsis and septic shock is characterized by left ventricular (LV) failure. To date, it is unclear whether clinically unrecognized myocardial cell injury accompanies, causes, or results from this decreased cardiac performance. We therefore studied the relationship between cardiac troponin I (cTnI) and T (cTnT) and LV dysfunction in early septic shock. METHODS: Forty-six patients were consecutively enrolled, fluid-resuscitated, and treated with catecholamines. Cardiac markers were measured at study entry and after 24 and 48 h. LV function was assessed by two-dimensional transesophageal echocardiography. RESULTS: Increased plasma concentrations of cTnI (>/=0.4 microgram/L) and cTnT (>/=0.1 microgram/L) were found in 50% and 36%, respectively, of the patients at one or more time points. cTnI and cTnT were significantly correlated (r = 0.847; P <0.0001). Compared with cTnI-negative patients, cTnI-positive subjects were older, presented higher Acute Physiology and Chronic Health Evaluation II scores at diagnosis, and tended to have a worse survival rate and a more frequent history of arterial hypertension or previous myocardial infarction. In contrast, the two groups did not differ in type of infection or pathogen, or in dose and type of catecholamine administered. Continuous electrocardiographic monitoring in all patients and autopsy in 12 nonsurvivors did not disclose the occurrence of acute ischemia during the first 48 h of observation. LV dysfunction was strongly associated with cTnI positivity (78% vs 9% in cTnI-negative patients; P <0.001). In multiple regression analysis, both cTnI and cTnT were exclusively associated with LV dysfunction (P <0.0001). CONCLUSIONS: These findings suggest that in septic shock, clinically unrecognized myocardial cell injury is a marker of LV dysfunction. The latter condition tends to occur more often in severely ill older patients with underlying cardiovascular disease. Further studies are needed to determine the extent to which myocardial damage is a cause or a consequence of LV dysfunction.

Acute generalized exanthematous pustulosis induced by paracetamol. A case with severe hemodynamic disturbances.

We report on a 28-year-old Bangladesh man with acute generalized exanthematous pustulosis, induced by paracetamol. The patient presented with an erythematous and pustular eruption after taking 1 tablet of paracetamol for a sore throat. After intravenous administration of propacetamol hydrochloride (which is a prodrug of paracetamol), the rash became worse, showing a toxic epidermal necrolysis-like appearance and the patient suffered from severe hemodynamic disturbances. After discontinuation of propacetamol hydrochloride, the eruption cleared within 2 days. Prick testing performed in the patient revealed a positive reaction for propacetamol hydrochloride.