Search

Since its inception some three decades ago the concept of intensive care underwent considerable changes: Firstly, the ICU has become a distinct hospital ward specifically built to allow the use of ultramodern technology and the execution of exhaustive protocols (infection control etc). Secondly, the patients admitted for therapy have evolved away from those suffering from the acute respiratory failure of neuromuscular insufficiency to encompass all clinical conditions representing a threat to life. Admission criteria have also changed and now include patients with poor or even no prognosis; the availability of an empty ICU bed often prompts the admission of a patient not requiring intensive care at all. Thirdly, costs have escalated enormously, second only to the operating suite as the most expensive clinical facility of the modern hospital. It is now estimated that as much as 20% of hospital resources are expended in the provision of ICU facilities for only 5% of total hospital admissions. Moreover, with an average rate of ICU mortality far exceeding 20%, a substantial sum of money is being invested to produce just one survivor.

Consumptive coagulation disorders are frequently observed in critically ill patients secondary to other underlying diseases. Initial hypercoagulability leads to subsequent hypocoagulability due to consumption of procoagulant proteins, inhibitors, and platelets. This process evolves in three distinct phases: an initial increase in coagulation activity is characterised by the activation of coagulation factors and platelets without any clinical symptoms of a haemorrhagic diathesis. The ongoing process of activation and accelerated consumption of coagulation factors and inhibitors causes a critical reduction in the haemostatic potential. The time of onset of the clinical symptoms of bleeding depends on the patient's underlying disease and its pharmacological management. Coagulation processes that are restricted locally under normal conditions become disseminated when the inhibitory potential--mainly represented by antithrombin III (AT III)--is exhausted. Therefore, thrombin formation occurs, especially in the microcirculation, where fibrin clot deposition begins to cause inhomogeneities of blood flow and thus to reduce oxygen delivery to the tissues. Hypocoagulability, reactive hyperfibrinolysis, and diffuse bleeding lead to an irreversible systemic breakdown of haemostatic mechanisms (disseminated intravascular coagulation, DIC). The laboratory diagnosis of accelerated consumption is based on the course of global coagulation tests (e.g., prothrombin time, activated partial thromboplastin time, platelet count) and more sensitive ("dynamic") activation parameters such as prothrombin fragment F1 + 2, thrombin-AT III complex, fibrin monomers, or d-dimer. Measurements of plasminogen, tissue plasminogen activator, plasminogen activator inhibitor 1, and alpha 2-antiplasmin-plasmin complex provide information on fibrinolytic turnover.(ABSTRACT TRUNCATED AT 250 WORDS)

This study compared the continuous positive airways pressure mode of the demand valve system of the Engstrom Erica ventilator with a custom-made continuous flow continuous positive airways pressure system in terms of the oxygen cost of breathing during weaning from mechanical ventilation. Ten consecutive patients in our intensive care unit, with thermodilution pulmonary artery flotation catheters in situ, were studied. Measurements were carried out under steady-state conditions, initially when breathing spontaneously with continuous positive airways pressure via the Erica and then when transition to the continuous flow system was achieved. There were no significant differences between the two methods of providing continuous positive airways pressure in terms of the measured and derived physiological variables studied, with the exception of oxygen consumption. Oxygen consumption with the continuous flow system was significantly less than with the Erica (142.8 (SEM 31.4) ml.min-1.m-2 compared with 165.8 (SEM 30.5) ml.min-1.m-2, p < 0.05). This difference reflects the reduced oxygen cost of breathing when the custom-made continuous flow system was used during weaning.

Patients with end-stage liver disease frequently develop combined coagulopathies due to increased procoagulant and fibrinolytic turnover as well as thrombocytopenia. The onset of clinical symptoms of a haemorrhagic diathesis requires balanced substitution of coagulation factors, since fresh frozen plasma alone does not always maintain a sufficient haemostatic potential in these patients. This substitution commonly follows standard rules based on the assumption that 0.5-1 IU of a coagulation factor or inhibitor concentrate given per kg body weight will increase its endogenous activity by 1%. We set out to investigate the validity of this standard regime in patients with end-stage liver disease scheduled for orthotopic liver transplantation.Fifty-one adult patients were prospectively studied. In 37 patients with antithrombin III (AT III) activity70%, an AT III preparation (Kybernin, Behring, Marburg, Germany) was given preoperatively (mean dose 2616 +/- 207 IU) following standard calculations in order to increase endogenous activity to 80%. Twenty-seven of the patients had chronic hepatic failure (CHF group) with histologically proven cirrhosis and 10 had acute hepatic failure (AHF group). Blood samples were drawn prior to a 15-min infusion of AT III concentrate and 30 min thereafter. In 14 patients with prothrombin time (PT)40%, AT III levels had been corrected earlier during the clinical course to achieve activities70%. Prothrombin complex (PPSB, Beriplex, Behring, Marburg, Germany) was substituted (mean dose 2304 +/- 289 IU) to increase procoagulant activity to PT60%. Blood samples were drawn in the same fashion as in the AT III group. The amounts of AT III and PPSB concentrates (delta AT III, [IU/kg]; delta PPSB [IU/kg]) required to increase AT III activity and PT, respectively, by 1% were calculated.Standard calculations for AT III substitution indicated AT III recovery in all 37 patients who received AT III concentrate. However, there was a statistically significant difference between patients with CLF and ALF. In patients with CLF, delta AT III was found to be 0.8 IU/kg (+/- 0.1 SEM) and in those with ALF it was 1.5 IU/kg (+/- 0.1 SEM) (P0.05, t-test). In patients treated with PPSB concentrate, delta PPSB was 1.6 U/kg (+/- 0.2 SEM) for both CLF and ALF groups.In patients with end-stage liver disease standard rules for substitution with AT III-concentrate are adequate only for patients with CLF. In patients with ALF higher AT III doses are required to achieve the expected effect on endogenous AT III activity. Procoagulant activity, as reflected by PT, can be increased by 1% when 1.6 IU/kg PPSB concentrate is given. However, this study shows the effects of coagulation concentrates only 30 min after administration. An increased volume of distribution and increased turnover may explain the poor recovery of AT III activity in the ALF group, indicating that the dose of coagulation concentrate should be estimated against the background of the patient's clinical symptoms and diagnosis.

Mercury in silastic strain gauge plethysmography (MSG) is a noninvasive method for assessing microvascular parameters in peripheral limbs. MSG allows measurement of capillary filtration coefficient (Kf), isovolumetric venous pressure (Pvi), venous pressure (Pv) and arterial inflow (Qa) into the limb, respectively. We used MSG in combination with invasive monitoring techniques (pulmonary artery flotation catheters and arterial catheters) to study 36 critically ill patients in either hemorrhagic or septic shock. We observed marked increases in Pvi in both patient groups which correlated with outcome. On admission, both groups showed elevated values for Pvi, survivors 37.7 +/- 2.6, nonsurvivors 33.7 +/- 3.5 mm Hg (mean +/- SEM) when compared with a control group of young healthy students (22.1 +/- 0.82 mm Hg). Survivors showed a decrease in Pvi to 27.3 +/- 1.7 mm Hg, whereas in nonsurvivors Pvi increased to 39.5 +/- 3.0 at the last measurement taken. The changes in Pvi depended on the resuscitation regime used. On admission, patients requiring only fluid replacement (F) had a lower Pvi (31.3 +/- 2.9 mm Hg) than patients needing inotropic support with dobutamine (D, Pvi = 38.2 +/- 2.4 mm Hg) to fulfill our therapeutic goals (DO2550 ml.min-1 x m-2, VO2150 ml.min-1 x m-2 and mixed venous lactate1.5 mmol/l). After treatment Pvi did not change significantly in the F group (31.3 +/- 1.8), the D group however showed a significant decrease in Pvi to 25.4 +/- 2.42, which did not differ from the normal value. We regard Pvi as an indicator of insufficient microvascular flow.(ABSTRACT TRUNCATED AT 250 WORDS)

Trauma, shock, and sepsis are frequently complicated by coagulation disorders which contribute to the development of multiorgan failure [1]. Especially in trauma patients, intrinsic and extrinsic activation of the clotting cascade is started by the release of tissue factor and contact activation following vascular damage. In septic patients, lipopolysaccharides (LPS) accelerate procoagulant turnover by activating neutrophils and hence mediators like elastase or platelet activating factor (PAF), and factor XII. The application of cristalloids and colloids in order to maintain normovolemia further dilutes both the procoagulant and inhibitor potential of the plasmatic coagulation. Plasma factors and platelets are lost by traumatic, surgical or diffuse bleeding. However, with ongoing activation of the coagulation cascade, dilution and loss become less important compared to changes in the dynamics of procoagulant and inhibitor turnover.

OBJECTIVE To evaluate a computer-based, real-time, multibreath nitrogen washout technique in mechanically ventilated patients, incorporating an in-line flow measurement device to measure functional residual capacity and two indices of gas mixing, ventilatory efficiency, and alveolar mixing efficiency. SETTING ICU, Charing Cross Hospital, London. DESIGN Within-patient reproducibility of a multibreath nitrogen washout technique. PATIENTS Seven intubated patients requiring mechanical ventilation. One patient completed two sets of readings. INTERVENTIONS Patients were connected to a pneumatically driven ventilator fitted with a switching device to be operated either by an appropriate oxygen-nitrogen mixture or equivalently blended oxygen-argon mixture. An inspiratory-expiratory, two-way valve was attached to the delivery port of the ventilator, with a pneumotachograph for flow measurement and a gas sampling probe for gas concentration measurement in line with the patient's endotracheal tube. The analog signals were digitized and handled by a microcomputer. MEASUREMENTS AND MAIN RESULTS No significant differences were found for any index, with coefficients of variation of 1.5%, 2.9%, and 2.1% for functional residual capacity, ventilatory efficiency, and alveolar mixing efficiency, respectively. CONCLUSIONS This method gives excellent reproducibility for biological measurements in a clinical setting and shows that these measurements can readily be made on mechanically ventilated patients.

To determine appropriate doses of ciprofloxacin and vancomycin for septic patients with acute renal failure (ARF) treated by continuous arteriovenous and venovenous haemodialysis, (CAVHD/CVVHD), we performed pharmacokinetic studies in patients receiving these antibiotics. All patients were treated by CAVHD/CVVHD using Hospal AN69S 0.43 m2 filters and Fresenius 1.5% peritoneal dialysis fluid at dialysate flow rates (Qd) of 1 and 2 l/h. Patients received ciprofloxacin 200 mg i.v. 12-hourly (n = 6) or 8-hourly (n = 5); vancomycin 1 g i.v. was administered to 10 patients approximately every 48 h to maintain therapeutic plasma levels. For ciprofloxacin, volume of distribution (Vdarea) was 136.5 +/- 9.81, terminal elimination half-life (t1/2) 6.4 +/- 0.8 h, and total body clearance (TBC) 264.3 +/- 22.9 ml/min (mean +/- SEM). Mean sieving coefficient (S/C) was 0.76 +/- 0.05 and filter clearances at Qd 1 and 2 l/h were 16.2 +/- 1.9 and 19.9 +/- 1.1 ml/min respectively. For vancomycin, Vdarea was 60.7 +/- 5.11, t1/2 24.7 +/- 2.6 h and TBC 31.0 +/- 4.6 ml/min. Mean S/C was 0.66 +/- 0.08 and filter clearances at Qd 1 and 2 l/h 12.1 +/- 2.0 and 16.6 +/- 2.0 ml/min. These data suggest that patients with ARF treated by CAVHD/CVVHD should be given ciprofloxacin 200 mg i.v. 8-12-hourly and vancomycin every 48 h.

To determine appropriate doses of ciprofloxacin and vancomycin for septic patients with acute renal failure (ARF) treated by continuous arteriovenous and venovenous haemodialysis, (CAVHD/CVVHD), we performed pharmacokinetic studies in patients receiving these antibiotics. All patients were treated by CAVHD/CVVHD using Hospal AN69S 0.43 m2 filters and Fresenius 1.5% peritoneal dialysis fluid at dialysate flow rates (Qd) of 1 and 2 l/h. Patients received ciprofloxacin 200 mg i.v. 12-hourly (n = 6) or 8-hourly (n = 5); vancomycin 1 g i.v. was administered to 10 patients approximately every 48 h to maintain therapeutic plasma levels. For ciprofloxacin, volume of distribution (Vdarea) was 136.5 +/- 9.81, terminal elimination half-life (t1/2) 6.4 +/- 0.8 h, and total body clearance (TBC) 264.3 +/- 22.9 ml/min (mean +/- SEM). Mean sieving coefficient (S/C) was 0.76 +/- 0.05 and filter clearances at Qd 1 and 2 l/h were 16.2 +/- 1.9 and 19.9 +/- 1.1 ml/min respectively. For vancomycin, Vdarea was 60.7 +/- 5.11, t1/2 24.7 +/- 2.6 h and TBC 31.0 +/- 4.6 ml/min. Mean S/C was 0.66 +/- 0.08 and filter clearances at Qd 1 and 2 l/h 12.1 +/- 2.0 and 16.6 +/- 2.0 ml/min. These data suggest that patients with ARF treated by CAVHD/CVVHD should be given ciprofloxacin 200 mg i.v. 8-12-hourly and vancomycin every 48 h.

Adverse changes in the microcirculation are currently considered as the most likely common pathway of organ failure, dramatically manifest in the multiple organ failure syndrome. We have investigated 28 patients presenting with gross cardiovascular instability due to septic shock or haemorrhage, using standard invasive methods of monitoring (Physiological Profile). We combined this study with a computer assisted mercury-in-rubber strain gauge plethysmography (MSG) measurement, for a parallel (non-invasive) assessment of peripheral microcirculatory function. We started the investigation on patient arrival in ICU and continued it during their resuscitation regime, which essentially consisted of fluid loading together with inotropic support, where necessary. We found highly significant changes in isovolumetric venous pressure (Pvi), determined by the MSG technique, when we compared survivors (27.29 +/- 1.65 mmHg, mean +/- s.e.m.) with non-survivors (39.5 +/- 2.97 mmHg, P less than 0.001). To investigate the role of dobutamine in patient improvement we compared the Pvi values obtained from the MSG studies and demonstrated a significant decrease from the initial value (38.2 +/- 2.4 mmHg) to the final one (25.4 +/- 2.4 mmHg), obtained after weaning the patients off dobutamine. Marked cyclic changes in limb circumference (vasomotion) were also observed and their appearance correlated well with accepted parameters of cardiovascular instability. We propose that changes in both Pvi and Vm are useful indices of microvascular hypoperfusion which is probably the underlying cause of pathology in both patient groups.

The development of multiple organ failure associated with sepsis has been attributed to a number of pathophysiological factors. A perfusion deficit [1] brings about local hypoxemia and reperfusion injury by oxygen radical formation [2–5] and endothelial wall damage [6] with ensuing leukocyte and macrophage sequestration in the microcirculation and release of mediators such as tumor necrosis factor (TNF) [7], phospholipase A2 [8], interleukins [9], complement factor [10], platelet activating factor [11], and proteases [12] which lead to cellular damage, altered microvascular permeability and hypoxia associated with hemodynamic instability. Endothelial cell damage is probably involved in the decrease in vascular reactivity to stimulation by adrenergic transmitters [13–15]. This primary cellular defect may be responsible for inadequate oxygen utilization [16]. Therapeutic maneuvers, which increase tissue perfusion or oxygen delivery, may either reduce the degree of anaerobic metabolism or increase lactate clearance producing a fall in blood lactate. This can be achieved by inotropic or vasodilator therapy.

To determine appropriate doses of cefuroxime and ceftazidime for septic patients with acute renal failure (ARF) treated by continuous arteriovenous haemodialysis (CAVHD), we performed pharmacokinetic studies in patients receiving these antibiotics. All patients were treated by CAVHD using Hospal AN69S 0.43 m2 filters and Fresenius 1.5% peritoneal dialysis fluid at dialysate flow rates (Qd) of 1 and 2 l/h. Patients received cefuroxime 500 mg (n = 11) or 750 mg (n = 1), or ceftazidime 500 mg (n = 9) i.v. 12-hourly and all studies were done at steady-state. For cefuroxime, volume of distribution (Vdarea) was 22.8 +/- 3.5 l, terminal elimination half-life (t1/2) 12.6 +/- 2.2 h and total body clearance (TBC) 22.3 +/- 3.0 ml/min (mean +/- SEM). Mean sieving coefficient (SC) was 0.90 +/- 0.12 and filter clearances at Qd 1 and 2 l/h were 14.0 +/- 2.3 and 16.2 +/- 3.4 ml/min respectively. For ceftazidime, Vdarea was 31.1 +/- 6.5 l, t1/2 14.7 +/- 3.3 h, and TBC 24.8 +/- 0.8 ml/min. Mean SC was 0.86 +/- 0.03, and filter clearances at Qd 1 and 2 l/h 13.1 +/- 1.2 and 15.2 +/- 1.5 ml/min. Satisfactory plasma concentrations of both antibiotics were maintained in all patients during treatment. These data suggest that cefuroxime 500-750 mg and ceftazidime 500 mg 12-hourly are suitable doses for patients with ARF treated by CAVHD.

Under normal physiological conditions, the supply of oxygen to the respiring tissues can be thought of as a finite series of demands within the tissues which generates the flow of oxygen from the ambient air to the oxygen consuming tissues [1]. As physical stress and the demand for oxygen as source of energy increases, provision is made for more oxygen to be transported by means of increased ventilation and recruitment of more alveoli (larger surface area for gas exchange), greater pulmonary blood flow and peripheral vasodilation in the tissues in question. Under those circumstances, the relationship of oxygen transport and oxygen consumption can be considered a straight line [2]. This is most evidently the case in exercising athletes where the need for oxygen creates the transport or delivery system to follow suit until the delivery system reaches its limits and the combustion of lactate via pyruvate ceases because of lack of oxygen, and lactic acidosis develops [3].

Duplex doppler examination of blood flow in renal interlobar arteries was analysed in twelve critically ill patients before and during low-dose dopamine infusion (2 μg/kg/min). Renal vasodilatation and increased blood flow were observed with dopamine, confirming results with indirect or invasive techniques. The doppler ultrasound technique is entirely non-invasive, is simple and quick to carry out, provides instant results, and will allow tailoring of inotropic support in critically ill patients to provide optimum renal blood flow.

Severe acute thallium poisoning in a young man is described. He presented with transient loss of consciousness and paraesthesiae of finger tips and lips, with a blood thallium concentration of 5750 micrograms/l (levels above 200 micrograms/l are toxic). He rapidly lost limb sensation and power and later required temporary mechanical ventilation and nasogastric feeding. The neurological sequelae one year afterwards are a flaccid paraparesis, cerebellar ataxia and mental impairment. Immediate cardiovascular complications included hypertension, sinus tachycardia, ECG abnormalities and an episode of ventricular fibrillation. We were able to assess the relative merits of different methods advocated for enhancing thallium excretion. Oral Prussian blue, forced diuresis and haemodialysis were found to be the most effective: 2000 mg of thallium were eliminated over 20 days, 820 mg over 46 days and 225 mg over 25 days respectively by these methods. Haemofiltration was ineffective. Diethyldithiocarbamate, a chelating agent, brought about a rise in serum thallium concentration accompanied by clinical deterioration and its use should be abandoned.

Severe acute thallium poisoning in a young man is described. He presented with transient loss of consciousness and paraesthesiae of finger tips and lips, with a blood thallium concentration of 5750 μg/l (levels above 200μg/l are toxic). He rapidly lost limb sensation and power and later required temporary mechanical ventilation and nasogastric feeding. The neurological sequelae one year afterwards are a flaccid paraparesis, cerebellar ataxia and mental impairment. Immediate cardiovascular complications included hypertension, sinus tachycardia, ECG abnormalities and an episode of ventricular fibrillation. We were able to assess the relative merits of different methods advocated for enhancing thallium excretion. Oral Prussian blue, forced diuresis and haemodialysis were found to be the most effective: 2000 mg of thallium were eliminated over 20 days, 820 mg over 46 days and 225 mg over 25 days respectively by these methods. Haemoflltration was ineffective. Diethyldithiocarbamate, a chelating agent, brought about a rise in serum thallium concentration accompanied by clinical deterioration and its use should be abandoned.

Continuous arteriovenous haemodialysis (CAVHD) is a new treatment for critically ill patients with renal failure that combines convective and diffusive solute removal. The clearance of urea (14·8-22·1 ml/min) is sufficient to achieve a steady-state urea concentration of 22 mmol/1, even in patients with a high catabolic rate and cardiovascular instability. The technique is simple and does not involve the use of blood pumps or specialised staff. Initial experience in 36 critically ill patients with renal failure indicates that it is safe and reliable, with less associated morbidity than other techniques.

Two patients were admitted directly to our Intensive Care Unit in acute respiratory failure due to pneumonia with septicaemic shock, renal and hepatic impairment. Sputum and blood cultures failed to grow any organisms and despite broad spectrum antibiotic therapy for 7 days, neither patient improved. Diagnosis of the rare pneumonic form of psittacosis was made following a raised titre. After treatment with tetracyclines, both patients made a rapid recovery. Retrospective direct questioning revealed that they had close contact with psitacine birds.