Organophosphorus pesticide poisoning: cases and developments.

Self-poisoning with organophosphate pesticides is a major health problem world-wide. Through the inhibition of acetylcholinesterase, organophosphorus poisoning is characterised by the clinical picture of acute cholinergic crisis. Other manifestations are the intermediate neurotoxic syndrome and delayed polyneuropathy. In the Western world, the occurrence of organophosphorus poisoning is less prevalent due to the declining availability of organophosphate pesticides, which could render the recognition of this particular type of intoxication and its specific treatment more difficult. In this article we discuss some recent developments and treatment dilemmas, illustrated by cases from our clinic, followed by a review of the current recommendations in the treatment of organophosphate poisoning.

[Serious intoxication with hydroxychloroquine, with haemodynamic instability: a case report supporting treatment with diazepam]. / Ernstige intoxicatie met hydroxychloroquine, met hemodynamische instabiliteit: casuistische ondersteuning voor behandeling met diazepam.

A 37-year-old woman was admitted to the emergency room because of an autointoxication with hydroxychloroquine, leading to haemodynamic instability. Treatment consisted of the rapid administration of intravenous diazepam, after which the hypotension recovered rapidly even though no vasoactive medication was given. Treatment with diazepam has been advised in the Netherlands for many years in case of severe hydroxychloroquine intoxication, despite the fact that convincing evidence for its use is lacking. On the basis of the experience with the relevant cases, the administration of diazepam, 2 mg/kg initially followed by 2 mg/kg/24 hours as a continuous infusion, should certainly be considered for supportive treatment in the ICU in case of severe haemodynamic instability.

A Systematic Review of the Effects of Hyperoxia in Acutely Ill Patients: Should We Aim for Less?

INTRODUCTION: Despite widespread and liberal use of oxygen supplementation, guidelines about rational use of oxygen are scarce. Recent data demonstrates that current protocols lead to hyperoxemia in the majority of the patients and most health care professionals are not aware of the negative effects of hyperoxemia. METHOD: To investigate the effects of hyperoxemia in acutely ill patients on clinically relevant outcomes, such as neurological and functional status as well as mortality, we performed a literature review using Medline (PubMed) and Embase. We used the following terms: hyperoxemia OR hyperoxemia OR ["oxygen inhalation therapy" AND (mortality OR death OR outcome OR survival)] OR [oxygen AND (mortality OR death OR outcome OR survival)]. Original studies about the clinical effects of hyperoxemia in adult patients suffering from acute or emergency illnesses were included. RESULTS: 37 articles were included, of which 31 could be divided into four large groups: cardiac arrest, traumatic brain injury (TBI), stroke, and sepsis. Although a single study demonstrated a transient protective effect of hyperoxemia after TBI, other studies revealed higher mortality rates after cardiac arrest, stroke, and TBI treated with oxygen supplementation leading to hyperoxemia. Approximately half of the studies showed no association between hyperoxemia and clinically relevant outcomes. CONCLUSION: Liberal oxygen therapy leads to hyperoxemia in a majority of patients and hyperoxemia may negatively affect survival after acute illness. As a clinical consequence, aiming for normoxemia may limit negative effects of hyperoxemia in patients with acute illness.

Life-threatening Pneumocystis jiroveci pneumonia following treatment of severe Cushing's syndrome.

We describe two patients with a severe Cushing's syndrome due to ectopic production of ACTH. Both patients developed a life-threatening Pneumocystis jiroveci pneumonia (PCP) shortly after treatment of the hypercortisolism was started by means of inhibition of production of glucocorticoids and glucocorticoid receptor blockade. We presume that the restored immune response elicited the clinical symptoms of the opportunistic, previously subclinical Pneumocystis jiroveci infection. The immunocompromised state and the delicate glucocorticoid balance in patients with a severe Cushing's syndrome necessitate a specific diagnostic and therapeutic approach.

[Again new resuscitation guidelines (2006): justification, costs and potential confusion]. / Weer nieuwe richtlijnen voor reanimatie (2006): onderbouwing, kosten en mogelijke verwarring.

The last revision of the Dutch resuscitation guidelines, a translation of the European Resuscitation Council Guidelines 2005, is based on the recommendations of the International Liaison Committee on Resuscitation (ILCOR). The previous Dutch guidelines were issued in 2002. Most changes are based on laboratory studies and retrospective analyses. The most important changes are: recognizing circulatory arrest on unresponsiveness and abnormal breathing; a new ratio of chest compressions to ventilations i.e. 30:2 instead of 15:2; and following the procedure of checking the airway (A), taking over the circulation (C) and breathing (B). Furthermore in the event of ventricular fibrillation or ventricular tachycardia with no pulsations then one defibrillator shock only is to be given; this is in contrast with the previous application of cycles of 3 shocks. The work and costs of implementation involved in the revision of resuscitation guidelines are tremendous, especially in view of the huge number of laypersons who need to be retrained. Also, frequent changes of guidelines may cause confusion and have a negative effect on the quality of resuscitation. Therefore, it is not evident that the benefits of this revision justify its costs. It would be good to prospectively evaluate the effectiveness and costs of this revision. In the future, these data might help to decide when altered international recommendations should be translated into new Dutch resuscitation guidelines. Alternative strategies should be considered, for example only changing the guidelines for advanced life support.

Serious envenomation after a snakebite by a Western bush viper (Atheris chlorechis) in the Netherlands: a case report.

Venomous snakebites are a rarity in the Netherlands. In this report we describe the case of a 26-year-old male amateur snakekeeper who was bitten in his left index finger by a Western bush viper (Atheris chlorechis). His clinical condition deteriorated rapidly with acute renal failure and considerable blood loss due to coagulopathy. Antidote was not readily available and was finally supplied by a zoo in Antwerp, Belgium. One day after admission the blood loss diminished.

Stridor and Horner's syndrome, weeks after attempted right subclavian vein cannulation.

A 23-year-old woman presented with renal failure resulting from polycystic kidney disease (PKD) aggravated by tubulo-interstitial nephritis. Emergency haemodialysis was planned, and cannulation of the right subclavian vein was attempted, but failed. During this procedure, inadvertent arterial puncture occurred. Transient mild ischaemia of the right arm, and a transient Horner's syndrome were noted. Seven weeks later she presented with severe stridor with impending respiratory failure necessitating emergency intubation; the right-sided Horner's syndrome had recurred. CT imaging showed a large pseudo-aneurysm of the brachiocephalic artery resulting in severe compression of the trachea. Using a prosthetic graft, the operation for the pseudo-aneurysm was successful; there were mild neurological sequelae. Although her family history was negative, autosomal dominant PKD should be considered, and we discuss the possible role of a pre-existing PKD-associated aneurysm.

Serotonin syndrome and rhabdomyolysis in venlafaxine poisoning: a case report.

Newer, more selective, antidepressant agents are increasingly being used as first-line treatment. However, clinical experience in patients after a deliberate overdose is limited. We present a case of venlafaxine intoxication complicated by a late rise in creatine kinase, seizures and serotonin syndrome. Rhabdomyolysis prolonged the hospital stay in our patient but had no other serious consequences. Physicians should be aware of this late phenomenon in patients with venlafaxine poisoning.

[Decisions around the end of life on Intensive Care: making the transition from curative to palliative treatment]. / Beslissingen rond het levenseinde op de Intensive Care: overgang van curatieve naar palliatieve behandeling.

The decision to move from curative treatment to palliative care in the intensive-care situation is less related to morals and ethics than it is to the assessment of medical issues, professionalism, communication and orchestration. Treatment should be considered medically pointless if, in the view of the treating physicians, it does not offer realistic chance to return to a meaningful life. Continuing futile care can be seen as disrespectful, both to the patient, his partner and the family, as well as to the members of the ICU team. Intensivists are responsible for withholding or withdrawing life support to patients in whom further life support is considered futile and who are unable to express their wishes due to critical illness and sedation. The intensivist typically makes this type of decision after a period in which medical and other information has been collected and after intensive discussions with other medical professionals as well as the partner and family. This is based on the trust that is built up through their skill, attitude and behaviour and that is perpetuated in a continuing process of intensive communication. Conflicts should be prevented, or at least recognised early and discussed. Ifa conflict is ongoing then it should be tackled by planning a number of consecutive consultations.

[The significance of elevated troponin levels in the absence of acute cardiac ischaemia]. / De betekenis van een verhoogde troponinewaarde zonder acute ischemische hartziekte.

Cardiac troponin I (cTnI) and cardiac troponin T (cTnT) are valuable heart markers in patients presenting with symptoms of ischaemic heart disease. A number of categories of patients frequently have raised concentrations of cardiac troponin (cTn) without having ischaemic heart disease. These include patients with heart diseases such as heart failure, myocarditis and valvular disease but also those with lung emboli, renal failure and sepsis. Possible underlying mechanisms are diffuse necrosis, cTn proteolysis or leakage of cytoplasmatic cTn with no irreversible damage to the contraction complex of heart-muscle cells. It is possible that cTn-measurement in patients with non-cardiac conditions is of prognostic value but so far this has only been demonstrated in dialysis patients and patients with pulmonary embolism.

Catecholamine dependency in a polytrauma patient: relative adrenal insufficiency?

A 65-year-old polytrauma patient was admitted post-operatively to the intensive care unit. His situation deteriorated with hemodynamic instability and continuous high fever. An infectious focus could not be found and repeated cultures remained negative. Empirical administration of antibiotics and changing of lines did not have any effect on the clinical picture. It was impossible to lower the dose of catecholamines because of repeated occurrence of hypotension, despite optimal hydration state and filling pressures. On the 15th day of admission intravenous hydrocortisone was started on suspicion of relative adrenal insufficiency. This action resulted in rapid hemodynamic recovery, disappearance of fever and enabled rapid tapering of the dose of noradrenaline. Incidence of relative adrenal insufficiency and diagnostic strategies are discussed in the population of critically intensive care patients.

Hormones in the critically ill patient: to intervene or not to intervene?

Critically ill patients show a variety of hormonal changes that appear to differ considerably in acute and prolonged critical illness. Whether these endocrine alterations serve as physiological adaptation or contribute to further deterioration remains an intriguing question. We review the recent literature and discuss whether measuring circulating hormone concentrations, performing stimulation tests, and intervening with hormone substitution could contribute to the recovery of critically ill patients.

Pharmacokinetics of cefpirome in critically ill patients with renal failure treated by continuous veno-venous hemofiltration.

OBJECTIVE: To study the cefpirome pharmacokinetics of patients with sepsis and multiple organ failure treated with CVVH. DESIGN: Measurements of serum and ultrafiltrate (UF) concentrations and in vitro sensitivity testing of isolated micro-organisms. SETTING: University hospital-based, single ICU. PATIENTS: Six critically ill CVVH-dependent patients with sepsis and multiple organ dysfunction syndrome in need of antimicrobial therapy. Age range: 60-75 years; APACHE II score for severity of illness on admission: 19-30. One patient survived. INTERVENTIONS: Cefpirome i.v. was started at 2 g in 30 min, then continued 1 g i.v.b.i.d. MEASUREMENTS: The UF rate was 27 +/- 7 ml/min on day 1 and 34 +/- 2 ml/min on day 2. Serum and ultrafiltrate samples were measured by a validated high performance liquid chromatography assay. Volume of distribution: 23 x 5(SD +/- 4 x 6) l. Total cefpirome clearance was 32 +/- 6 x 3 ml/min; cefpirome CVVH clearance (ClCVVH): 17 +/- 4.2 ml/min; mean serum half-life (t1/2): 8.8 +/- 2.3 h; mass transfer on day 1: 660 +/- 123 mg/12 h (33 +/- 6% of administered dose) and day 2: 642 +/- 66 mg/12 h (64 +/- 7%). Estimated sieving coefficient (ClCVVH/UF rate): 64 +/- 11%. In vitro sensitivity of isolated microbes was excellent except for two non-sensitive enterococci and Candida spp. CONCLUSIONS: The sieving coefficient (64%) indicates that a substantial fraction of the drug is not filtered; clearance by pathways other than CVVH mounted to 50% of the total clearance and increased on day 2, indicating that the dosing schedule used is appropriate for this setting. Cefpirome appeared to be safe in these patients and effective for most of the nosocomial microbial isolates. During more than 90% of the time, serum levels were maintained above killing concentrations for susceptible micro-organisms.

Hyperglycemia-induced hyperinsulinemia acutely lowers plasma apolipoprotein B but not lipoprotein (a) in man.

Acute hyperinsulinemia lowers plasma apolipoprotein B (apo B) and triglycerides by suppressing hepatic lipoprotein secretion and probably by enhancing catabolism of triglyceride-rich lipoproteins, but the effect of acute hyperinsulinemia on the plasma lipoprotein(a) (Lp(a)) level is unclear. We measured plasma triglycerides, cholesterol, apo B and Lp(a) in response to 3 h hyperglycemia-induced hyperinsulinemia (blood glucose clamped at 10 mmol/l) in 16 subjects (eight women and eight men). In a control experiment saline was infused in another group of seven men. After 3 h of hyperinsulinemia plasma triglycerides decreased by 29 +/- 14% (mean +/- S.D., P < 0.001) and this fall differed from the unchanged triglyceride level during saline infusion (P < 0.001). Plasma cholesterol fell by 8 +/- 5% (P < 0.001), which was different from the unchanged cholesterol during saline infusion (P < 0.02). Plasma apo B decreased by 9 +/- 8% (P < 0.001), which was again different from the minor fall in apo B (3 +/- 2%) during saline infusion (P < 0.02). However, plasma Lp(a) remained unchanged during hyperinsulinemia (change 8 +/- 15%, n.s.), as well as during saline infusion (change 5 +/- 15%, n.s.). The % change in apo B exceeded the % change in Lp(a) during hyperinsulinemia (P < 0.01). Baseline Lp(a) was inversely correlated with first phase insulin secretion (P < 0.05), but its level during the clamp was not related to insulin sensitivity. This study demonstrates that acute hyperglycemia-induced hyperinsulinemia has a different effect on plasma apo B and Lp(a) in healthy subjects. The present data support the notion that Lp(a) is metabolized differently from triglyceride-rich lipoproteins.

No deterioration of insulin secretion by the potassium channel opener pinacidil in essential hypertension.

Hypertension has been associated with hyperinsulinemia and insulin resistance. The elevations in plasma insulin are the apparent adaptation of the pancreatic beta cell to the resistance to insulin. Maintenance of normal insulin release is therefore of great importance for subjects with hypertension. The potassium channel opener pinacidil has antihypertensive properties. Pinacidil has been shown to inhibit Insulin release in vitro in isolated pancreatic beta cells. We therefore studied the acute effect of pinacidil on insulin secretion and insulin sensitivity in hypertensive and control subjects. The acute effect of pinacidil (25 mg, orally) on plasma insulin was studied during a hyperglycemic clamp (180 min, blood glucose 10 mmol/L) in 10 healthy volunteers and in 10 non-obese hypertensive patients in a randomised, placebo controlled double blind study. Fasting plasma insulin levels were 54.8 +/- 10.9 and 51.1 +/- 8.8 pmol/L in the control group and statistically significantly higher in the hypertensive group: 90.5 +/- 16.6 and 100.0 +/- 16.2 pmol/L (with and without pinacidil, respectively, both P < 0.02 vs control group). Plasma insulin levels rose to maximum levels of 246.7 +/- 44.6 and 267.2 +/- 56.2 pmol/L after 5 min in the control group (with and without pinacidil, respectively, NS) and to maximum levels of 248.9 +/- 37.3 and 238.0 +/- 39.1 pmol/L after 5 min in the hypertensive group (with and without pinacidil, respectively, NS). Areas under the insulin curve (AUCinsulin) of the first and second phase did not differ between the control and hypertensive group, with or without pinacidil. In the control and the hypertensive group separately no statistically significant effect of pinacidil on the mean glucose infusion rate/mean insulin level (M/I) ratio, a measure for insulin sensitivity, was shown. When both groups were taken together, an increase in the M/I ratio under the influence of pinacidil was found for the third hour of the clamp (P < 0.02). In conclusion, fasting insulin levels in the hypertensive subjects were significantly higher than in the control subjects. The potassium channel opener pinacidil did not influence insulin secretion in hypertensive patients and healthy controls. Pinacidil may have an enhancing effect on insulin sensitivity.

Pulmonary vasculitis may obscure large cell lung carcinoma. A case report.

Several vasculitic syndromes are recognized as paraneoplastic syndromes of an underlying malignant disease. Most frequently small vessel vasculitis of the skin has been reported. We describe the case of a 62-year-old man with a pulmonary mass due to pulmonary vasculitis. After resection of the pulmonary mass, the patient displayed bone metastasis. Retrospectively, tumor cells were found in the pulmonary mass that had been resected 9 months before. In this case report the rare association of vasculitis and lung carcinoma is reviewed. Our report indicates that pulmonary vasculitis may obscure the histologic findings of lung carcinoma and that in patients with localized pulmonary vasculitis special attention has to be paid to the possible presence of malignant cells.

The vanishing heart--deterioration on chest radiography with clinical improvement during prone position ventilation.

Prone position ventilation is used in the treatment of ARDS. Its beneficial effects are due to increased ventilation of the dorsal lung areas. Consequently, the now dependent parts of the lungs collapse, resulting in decreased sharpness of the cardiac silhouette. The latter may be misinterpreted as a worsening of the cardiopulmonary condition while, in fact, gas exchange and ventilation may be markedly improved. These features are illustrated in the case presented.

Clinical relevance of ATP-dependent potassium channels.

Many cells are equipped with so-called potassium (K+) channels which have an important role in maintaining transmembrane potential. Closure of these channels leads to membrane depolarization, which can be followed by cell-specific activity such as contraction of vascular smooth muscle, or secretion of insulin from pancreatic beta-cells. Therefore, it is not surprising that a number of drugs have been introduced which influence K+ channels by either blocking or opening them. The treatment of type 2 (non-insulin-dependent) diabetes mellitus with sulphonylurea derivatives (SU), which exert their insulinotropic effect by closing the K+[ATP] channels of the pancreatic beta-cell, is customary. Slight differences are described in the insulinotropic action of the various SU. Claims in the past that treatment with SU increases cardiovascular mortality are not supported by sound evidence. SU may even reduce cardiovascular mortality by protecting against ventricular arrhythmias during cardiac ischaemia. K+[ATP]-channel-opening drugs are under investigation for the treatment of essential hypertension and angina pectoris. They are at least as effective in achieving adequate blood pressure control as calcium channel blockers. The recently introduced coronary vasodilating drug, nicorandil, exerts its effect by two mechanisms of action: opening K+[ATP] channels in vascular smooth muscle cells of coronary arteries and activation of guanidyl cyclase by its nitro-group in these cells. A proarrhythmic effect of K+[ATP] channel openers has only been observed at very high doses, but not in the low doses used in angina pectoris and hypertension. In vivo no negative effect of K+[ATP]-channel-opening drugs on insulin secretion is found.

Non-conventional mechanical ventilation in severe ARDS, illustrated by a complicated case.

When conventional respiratory strategies fail to maintain adequate oxygenation treatment of severe ARDS is largely empirical. Modern techniques such as inverse ratio ventilation, permissive hypercapnia, NO inhalation and lowering tidal volumes/pressures are advocated. We report on a patient with severe ARDS who showed all the complications of the disease. The risks and benefits of (non)conventional ventilatory strategies are discussed and illustrated.

Prevention of hypotension after induction of anesthesia after preoperative tune-up. A preliminary report of the Groningen Tune-up Study.

OBJECTIVE: To investigate whether the frequently occurring hypotension after induction of anesthesia can be prevented by preoperative treatment at the ICU guided by hemodynamic data obtained from a pulmonary artery (PA) catheter. DESIGN: Prospective controlled open randomized single center study. SETTING: University tertiary referral hospital. PATIENTS: Thirty-one patients undergoing major vascular- or abdominal surgery. INTERVENTIONS: Patients were randomized to either the control group or the ICU group. Patients allocated for the ICU group were admitted to the ICU the day before the operation and treatment was started aimed at a CI > or = 4.0 l/min/m2. No special treatment was given to the control group the day before the operation. Anesthesia was induced with etomidate, rocuronium and sufentanil. MEASUREMENTS AND MAIN RESULTS: Seventeen patients were allocated for the control group and 14 for the ICU-group. Mean ages were 65 +/- 2.5 and 66 +/- 2.5 years, respectively. Both groups were comparable regarding age, sex, blood pressure and type of operation. Filling pressures at admission on the ICU were: central venous pressure 3 +/- 2 mm Hg and pulmonary capillary wedge pressure 8 +/- 3 mm Hg while CI was 3.2 +/- 0.8 l/min/m2. The hemodynamic goal was achieved in all 14 patients of the ICU-group preoperatively with a background infusion of three l/24 h crystalloids, after a mean infusion of 1623 +/- 552 ml colloids, and in seven patients a median dose of 3 micrograms/kg/min (range 2-6) dopamine. Blood pressure before induction was comparable in both groups. The fall in systolic BP 10 min after induction of anesthesia was 22 +/- 18 in the ICU-group versus 41 +/- 17 mm Hg in the control group (p = 0.004). The fall in diastolic BP was 11 +/- 6 mm Hg in the ICU group versus 25 +/- 11 mm Hg in the control group (p = 0.0003). No differences between the groups in changes of heart rate were observed: a decrease of 13 +/- 7 bpm (95% confidence intervals 8.5 to 17.0) in the ICU group versus 15 +/- 14 (95% confidence intervals 7.6 to 21.9) bpm in the control group (p = 0.6). CONCLUSIONS: Hypotension after induction of anesthesia is significantly attenuated by preoperative treatment aiming at a CI > or = 4.0 l/min/m2 in high risk patients planned for major vascular- or abdominal surgery.