Regulatory role for macrophage migration inhibitory factor in acute respiratory distress syndrome.

Migration inhibitory factor (MIF) is known to exert significant pro-inflammatory effects and has the potential to override the anti-inflammatory action of glucocorticoids. In this study we have identified significant quantities of MIF in the alveolar airspaces of patients with acute respiratory distress syndrome (ARDS). We show in alveolar cells from patients with ARDS that MIF augments pro-inflammatory cytokine secretion (TNF alpha and IL-8), anti-MIF significantly attenuates TNF alpha and IL-8 secretion and MIF overrides, in a concentration-related fashion, the anti-inflammatory effects of glucocorticoids. These findings suggest that MIF may act as a mediator sustaining the pulmonary inflammatory response in ARDS and that an anti-MIF strategy may represent a novel therapeutic approach in inflammatory diseases such as ARDS.

Minimally invasive surgical management of pelvic-ureteric junction obstruction: update on the current status of robotic-assisted pyeloplasty.

BACKGROUND: Pelvi-ureteric junction (PUJ) obstruction is characterized by a functionally significant impairment of urinary transport caused by intrinsic or extrinsic obstruction in the area where the ureter joins the renal pelvis. The majority of cases are congenital in origin; however, acquired conditions at the level of the ureteropelvic junction may also present with symptoms and signs of obstruction. Historically, open pyeloplasty and endoscopic techniques have been the main surgical options with the intent of complete excision or incision of the obstruction. The advent of laparoscopy and robotic-assisted applications has allowed for minimally invasive reconstructive surgery that mirrors open surgical techniques. AIMS We review the current status of robotic-assisted laparoscopic pyeloplasty and report on the result, continuing evolution, and potential role for this surgical procedure. MATERIALS AND METHODS: A review of the recent literature encompassing laparoscopic and robotic-assisted pyeloplasty was conducted with particular attention to operative techniques, surgical outcomes, and complication rates. RESULTS: Laparoscopic and robotic-assisted approaches are able to duplicate the open technique, and not surprisingly, are now being shown to be as efficacious as the gold standard open approach. The laparoscopic remains technically challenging due to the high proficiency level required for intracorporeal suturing, although added experience has resulted in shorter operative times. The advent of robotics has further expanded the breadth of this reconstructive procedure while preserving the benefits of decreased pain, shorter hospitalization, rapid convalescence, and an improved cosmetic result. DISCUSSION: The introduction of robotics to the field of minimally invasive surgery facilitates this procedure and may allow for more widespread implementation by surgeons of varying skill levels. These benefits must be balanced against the increased costs of the robotic platform. CONCLUSION: Clinical reports have demonstrated that robotic-assisted pyeloplasty is a safe, feasible, and effective technique for treating ureteropelvic junction obstruction in short term studies. Additional studies with prolonged follow-up will ultimately provide valuable information as to the long-term efficacy of robotic-assisted laparoscopic pyeloplasty.

Vascular anomalies during laparoscopic renal surgery: incidence and management of left-sided inferior vena cava.

BACKGROUND: Left-sided inferior vena cava (IVC) is an unusual abnormality that may be clinically significant during renal surgery. METHODS: We report the unique case of a patient with a centrally located left renal mass who underwent laparoscopic radical nephrectomy. During the hilar dissection, unusual vascular anatomy was encountered. The patient was noted to have a left-sided inferior vena cava with multiple renal veins and anomalous tributaries. Laparoscopic radical nephrectomy was performed without complication. DISCUSSION: The embryology of a left-sided inferior vena cava is reviewed, and the safety and feasibility of a laparoscopic approach is discussed.

Adrenal-preserving minimally invasive surgery: update on the current status of laparoscopic partial adrenalectomy.

Adrenalectomy is the standard of care for hormonally active adrenal masses. In recent years, minimally invasive laparoscopic excision has become a preferred management option. As with advances in parenchymal-sparing renal surgery, investigators have begun to examine adrenal-sparing procedures to preserve functional adrenal tissue. This article reviews the recent literature and reports on intermediate results with laparoscopic partial adrenalectomy (LPA).

Acute liver failure following therapeutic paracetamol administration in patients with muscular dystrophies.

Clinically significant liver damage in patients taking therapeutic doses of paracetamol is very rare. We report two cases of fulminant hepatic failure caused by therapeutic (4 g x day(-1)) paracetamol administration on our Intensive Care Unit. Both patients had a muscular dystrophy and presented with a chest infection on a background of endstage neuromuscular respiratory failure. We also noted one further similar case in the literature and suggest a relationship between muscular dystrophy and paracetamol-induced hepatotoxicity. In this report we discuss in detail possible mechanisms that may account for this apparent association, which include altered pharmacokinetics, reduced glutathione stores, malnutrition and hypoxic injury.

Extra-adrenal pheochromocytoma: diagnosis and management.

Extra-adrenal pheochromocytomas (EAPs) may arise in any portion of the paraganglion system, though they most commonly occur below the diaphragm, frequently in the organ of Zuckerkandl. EAPs probably represent at least 15% of adult and 30% of childhood pheochromocytomas, as opposed to the traditional teaching that 10% of all pheochromocytomas are at extra-adrenal sites. They may be malignant in up to 40% of the cases, though conflicting data add to the uncertainty of this point. Patients with EAPs may present with headache, palpitations, sweating, or hypertension. A small percent of patients may also be asymptomatic at presentation due to nonfunctional tumors. The diagnosis is confirmed by demonstrating elevated blood and urine levels of catecholamines and their metabolites. Imaging studies to evaluate for EAPs include CT, MRI, and (131)I-labelled metaiodobenzylguanidine scintigraphy. Preoperative pharmacologic preparation, attentive intraoperative monitoring, and aggressive surgical therapy have important roles in achieving successful outcomes. Recent reports suggest that a laparoscopic approach, along with intraoperative ultrasound, can safely remove these tumors. EAPs recur and metastasize more often than their adrenal counterparts, making lifelong follow-up essential.

The insulin response to intravenous fructose in maturity-onset diabetes mellitus and in normal subjects.

Insulin responses to intravenous fructose and glucose were measured in 15 patients with maturity-onset diabetes mellitus. In eight patients given fructose first the insulin responses to fructose and glucose were similar. In seven patients given glucose first the insulin response to subsequently infused fructose was significantly greater than to glucose. Multiple regression analysis showed that the ratio of the fructose to glucose insulin response, assessed by area under the insulin serum concentration-time curve (F/G ratio) in individual patients, correlated most closely with prefructose infusion plasma glucose. Similar analysis, applied to results in 27 normal subjects, showed that the most important determinant of the insulin response to fructose in this group also was the immediate prefructose infusion plasma glucose. Thus in diabetics, as in normal controls, the response of the beta cell to intravenous fructose appears to be sensitively set by the ambient plasma glucose concentration at the onset of fructose infusion.

Encephalitis lethargica.

We report a case of encephalitis lethargica, who presented major intensive care problems, particularly with respect to hyperirritability and convulsions, but who went on to complete recovery. This case would encourage a more aggressive attitude to the management of encephalitis.

Haemodynamic changes in neurogenic pulmonary oedema: effect of dobutamine.

The haemodynamic and gas exchange abnormalities occurring in neurogenic pulmonary oedema (NPO) were examined retrospectively in 20 patients admitted to the Intensive Therapy Unit (ITU) over a 45-month period (February 1992 to November 1995). In 12 patients, where vasoactive therapy with dobutamine was employed, its effect on haemodynamics was examined. Cardiac index (CI median 2.2 l min-1 m-2) and left ventricular stroke work index (LVSWI 20 g.m.m-2) were markedly depressed, while pulmonary artery wedge pressure (PAWP 17 mmHg), mean pulmonary artery pressure (MPAP 30.5 mmHg), systemic vascular resistance index (SVRI 2852 dyne.s.cm-5.m2) and pulmonary vascular resistance index (PVRI 393 dyne.s.cm-5.m2) were substantially elevated above normal values. Mean arterial pressure (MAP 82.5 mmHg) and heart rate (HR 102 bpm) were within normal limits. The poor oxygenation is indicated by a median PaO2/fiO2 ratio of 18.0 kPa. Patients treated with dobutamine showed significant increases in CI and LVSWI and significant falls in SVRI and PAWP at 2 and 6 h after institution of therapy, and there was a significant rise in PaO2/fiO2 ratio to 27.8 kPa at 6 h. NPO was generally associated with severe depression of myocardial function and elevation of pulmonary vascular pressures. This dysfunction was readily reversed by dobutamine.

Pulmonary and cardiac sequelae of subarachnoid haemorrhage: time for active management?

Cardiac injury and pulmonary oedema occurring after acute neurological injury have been recognised for more than a century. Catecholamines, released in massive quantities due to hypothalamic stress from subarachnoid haemorrhage (SAH), result in specific myocardial lesions and hydrostatic pressure injury to the pulmonary capillaries causing neurogenic pulmonary oedema (NPO). The acute, reversible cardiac injury ranges from hypokinesis with a normal cardiac index, to low output cardiac failure. Some patients exhibit both catastrophic cardiac failure and NPO, while others exhibit signs of either one or other, or have subclinical evidence of the same. Hypoxia and hypotension are two of the most important insults which influence outcome after acute brain injury. However, despite this, little attention has hitherto been devoted to prevention and reversal of these potentially catastrophic medical complications which occur in patients with SAH. It is not clear which patients with SAH will develop important cardiac and respiratory complications. An active approach to investigation and organ support could provide a window of opportunity to intervene before significant hypoxia and hypotension develop, potentially reducing adverse consequences for the long-term neurological status of the patient. Indeed, there is an argument for all SAH patients to have echocardiography and continuous monitoring of respiratory rate, pulse oximetry, blood pressure and electrocardiogram. In the event of cardio-respiratory compromise developing i.e. cardiogenic shock and/or NPO, full investigation, attentive monitoring and appropriate intervention are required immediately to optimise cardiorespiratory function and allow subsequent definitive management of the SAH.

Outcome of long-stay intensive care patients.

OBJECTIVES: To assess the numbers, characteristics and outcome for patients requiring long-term intensive care. DESIGN AND SETTING: Observational cohort study in 23 Scottish intensive care units over a 3-year period. PATIENTS AND PARTICIPANTS: 323 patients with an ICU stay of 30 days or more. MEASUREMENTS AND RESULTS: Although representing only 1.6% of patients, those with long stays occupied 15.7% of bed-days. Hospital survival among these patients was 59.9%. With the available data it was not possible to discriminate survivors from non-survivors. CONCLUSIONS: Since these patients have a relatively high hospital survival, resources should not be withheld from them on the basis of prolonged ICU stay alone, even in countries with limited ICU provision.

Acute amiodarone-induced lung toxicity.

OBJECTIVE: To investigate any relationship between the pathological features of amiodarone-induced pulmonary toxicity (APT) and clinical use of amiodarone in patients dying from acute respiratory distress syndrome (ARDS). DESIGN: Retrospective study. Review of clinical and pathological findings of patients dying from ARDS. SETTING: Intensive Care Unit (ICU) and Pathology Department of University hospital. SUBJECTS: Ten patients with clinical diagnosis of ARDS, who died in ICU and underwent post mortem examination. INTERVENTIONS: Case note review of clinical details; independent review of histological specimens. MEASUREMENT AND RESULTS: Over a 3-year period, ten patients underwent post mortem examination, of whom seven had received amiodarone. Three patients who received longer than 48 h of amiodarone had histological changes of widespread lipoid pneumonia, a recognised pattern of APT. CONCLUSIONS: Acute amiodarone pulmonary toxicity is a definite pathological entity in ICU patients. High oxygen concentrations may be a risk factor, while pre-existing pathology, e. g. ARDS, may mask its development. Amiodarone should be used with caution in this group of patients.

Profound reduction in morphine clearance and liver blood flow in shock.

In six patients with septic shock apparent liver blood flow was significantly reduced compared with two patients restudied on recovery from shock and a group of four matched unshocked patients undergoing intensive care (287 +/- 23 ml/min vs 870 +/- 164 ml/min; mean +/- SEM). In the shocked patients the elimination half-life of morphine was significantly prolonged (13.2 +/- 3.5 h vs 5.9 +/- 1.4 h; mean +/- SEM) and the systemic clearance of morphine reduced by 53%, in comparison with the non-shocked patients. In both groups, morphine elimination was markedly delayed compared with previously reported observations in normal subjects and surgical patients. Care should be exercised with the use of drugs with a high hepatic extraction ratio in shocked patients.

The haemodynamic effects of intermittent haemofiltration in critically ill patients.

The haemodynamic effects of intermittent high volume venovenous haemofiltration were studied in 13 critically ill patients. The mean negative fluid balance during filtration was 1.21 and the mean duration of treatment 3 h 40 min. The cardiac index fell initially (4.5 +/- 0.2 to 3.8 +/- 0.21/min/m2; p less than 0.05) but then remained stable throughout treatment before returning to baseline at the end of haemofiltration. The mean arterial pressure was unchanged with an increase in the systemic vascular resistance (651 +/- 33 to 765 +/- 65 dyne.s/cm5; p less than 0.05) suggesting that vascular responsiveness is maintained during haemofiltration.

Endothelin production in sepsis and the adult respiratory distress syndrome.

OBJECTIVE: Septic shock is characterised by a decrease in systemic vascular resistance. Nevertheless, regional increases in vascular resistance can occur which may predispose to organ dysfunction, including the adult respiratory distress syndrome (ARDS). Because endothelial damage is a major feature of acute lung injury, we examined whether the potent endothelial vasoconstrictor peptide endothelin-1 plays a pathophysiological role in sepsis or ARDS. DESIGN: Plasma endothelin was measured in mixed venous, pulmonary capillary and arterial blood, and the relationship with outcome measures was determined. SETTING: The intensive care unit of a university teaching hospital. PATIENTS AND PARTICIPANTS: A consecutive series of well-characterised patients with sepsis syndrome, both with (n = 11) and without (n = 15) ARDS, and ventilated controls without sepsis or ARDS (n = 7). MEASUREMENTS AND RESULTS: Plasma endothelin was significantly elevated in patients with sepsis alone and in patients with sepsis and ARDS. Plasma endothelin did not differ among mixed venous, pulmonary capillary and systemic arterial blood. On multiple regression analysis, plasma endothelin correlated positively with organ failure score and with oxygen consumption, and negatively with the PaO2 : FiO2 ratio. There was no correlation with plasma creatinine, suggesting that decreased renal clearance did not account for the high plasma endothelin concentrations. CONCLUSIONS: Although the lung does not appear to be the major site of endothelin production in critically ill patients with sepsis, increased endothelin production may contribute to regional increases in vascular [correction of vacular] resistance, hyperfusion, and the development of organ failure, including ARDS, in patients with sepsis.

Adrenaline in treatment of septic shock: effects on haemodynamics and oxygen transport.

The effects of adrenaline on haemodynamics and oxygen transport were studied in 13 patients with septic shock persisting after optimal fluid loading. Adrenaline was administered by intravenous infusion at an increasing dose until no further benefit was seen. There were significant increases in mean arterial pressure, cardiac index, left ventricular stroke work index and oxygen delivery index. There was no significant change in oxygen consumption although the trend was towards an increase. There was a significant reduction in oxygen extraction ratio, but no change in shunt fraction. Adrenaline would appear to have beneficial haemodynamic effects in septic shock.

Cross infection in an intensive care unit by Klebsiella pneumoniae from ventilator condensate.

Klebsiella pneumoniae serotype K28 was cultured from six patients over 5 weeks in a general Intensive Care Unit. Colonized condensate in the ventilator expiratory water traps was the probable source of the organism, and hand carriage the vehicle of transmission. Although the cross-infection hazard of ventilator tubing condensate is recognized, there is no report in the literature of an outbreak caused by such fluid. Ventilator tubing condensate should be viewed as contaminated clinical waste and dealt with accordingly.

Bioavailability, pharmacokinetics, and analgesic activity of ketamine in humans.

The pharmacokinetics of ketamine in analgesic doses after intravenous, intramuscular, and oral administration was investigated in healthy volunteers. Plasma ketamine concentration-time curves were fitted by a two-compartment open model with a terminal half-life of 186 min. Absorption after intramuscular injection was rapid and the bioavailability was 93%. However, only 17% of an oral dose was absorbed because of extensive first-pass metabolism. Simultaneous measurements of the elevation of pain threshold in an ischemic exercise test showed a marked effect for 15-60 min after intramuscular injection, but little or no effect after the oral solution. Pain threshold elevation occurred at plasma ketamine concentrations above 160 ng/ml.

Reversal of midazolam sedation with flumazenil following conservative dentistry.

The purpose of this double-blind randomized study was to assess recovery of mental function following reversal of midazolam-induced sedation with the specific antagonist flumazenil (R015-1788) or placebo following conservative dental procedures. Recovery was assessed using choice reaction time and critical flicker fusion threshold, both objective tests of psychomotor function; linear analogue sedation scores and simple memory tests. Assessments were repeated up to 3 h after administration of flumazenil or placebo to discover whether recovery was sustained or whether resedation occurred due to the short duration of action of flumazenil. Flumazenil in doses from 0.5 to 1.0 mg rapidly reversed the sedative and amnesic effects of a mean dose of 8.2 mg of midazolam without apparent evidence of subsequent resedation. Since recovery of mental function in the control group had ordinarily occurred 45 min after administration of placebo, routine reversal of midazolam sedation with flumazenil cannot be justified. Nevertheless, in cases of undue sedation persisting after dental treatment, flumazenil may be used with minimal risk of resedation occurring.

Impact of early endovascular aneurysmal occlusion on outcome of patients in poor grade after subarachnoid haemorrhage: a prospective, consecutive study.

Patients in poor grade (WFNS IV and V) after aneurysmal subarachnoid hemorrhage (SAH) often have a bad outcome. To evaluate early GDC embolisation on such patients a prospective observational study, with comparison to a historical cohort was performed. From January 1996 to December 1998 113 patients were admitted to the Department of Clinical Neurosciences in poor grade after SAH (45 WFNS IV and 68 WFNS V). Eighty-one patients were managed actively with endovascular occlusion of the aneurysm (n = 42) where possible and delayed clipping (n = 16) where not. On an intention to treat basis, 46% had a favourable outcome (Glasgow Outcome Score IV or V) and 48% had died by 3 months. Compared to an historical cohort managed in the same unit between 1992 and 1995 (n = 62, 52% favourable outcome) these results suggest that early GDC aneurysmal occlusion has had a minimal impact on overall outcome.