Systemic capillary leak syndrome. Case report.

We here report the case of a patient with systemic capillary leak syndrome (SCLS). This syndrome is a rare condition characterized by recurrent episodes of hypotension with hemoconcentration and hypoproteinemia. It is due to unexplained episodic capillary hyperpermeabilty that results in fluid and protein shift from the intravascular to the interstitial space: generalized edema, shock and renal failure follow. A 59 yo man was admitted to our intensive care unit because of unexplained shock with hemoconcentration, renal failure, and metabolic acidosis. Previous attemps to reverse shock in a medical ward with crystalloids and dopamine failed. An abdominal CT scan, a TEE, and chest X ray study were inconclusive. No sign or history of major infections or anaphylaxis were present. The patient was resuscitated with massive fluid infusions and norepinephrine on the guide of a Swan Ganz catheter. The diagnosis was made on the basis of a previous episode of severe shock complicated with renal failure and a compartment syndrome, the hemoconcentration, and the negative cardiopulmonary findings. A small amount of monoclonal immunoglobulin G, kappa chain, found in the serum confirmed the diagnosis. The SCLS should be considered in the differential diagnosis of idiopathic and anaphylactic shock. Patients may benefit from a prophylactic treatment with theophilline and terbutaline.

Delayed upper airway obstruction following a retropharyngeal haematoma after minor head trauma.

The development of a retropharyngeal haematoma may occur rarely after major head, face or cervical spine injuries, and it is even less frequent following minor trauma. As these patients are commonly not intubated, a life-threatening upper airway obstruction may occur. We report the case of a man who experienced a late retropharyngeal haematoma with delayed, progressive upper airway obstruction after a minor frontal wound. After an emergency intubation a nuclear magnetic resonance highlighted the magnitude of the bleeding into the retropharynx accounting for the slow onset of the symptoms. Predisposing factors such as antithrombotic therapies and vascular lesions may enhance the risk of occurrence even after minor trauma. Hypotheses on how to identify this potentially fatal complication earlier are reported.

Pharmacokinetic profile of the induction dose of propofol in chronic renal failure patients undergoing renal transplantation.

STUDY OBJECTIVE: To define the pharmacokinetic profile of the induction dose of propofol in chronic renal failure patients. DESIGN AND SETTING: Determination of propofol blood concentrations after the bolus dose of 2 mg.kg-1 bw injected in 30 seconds in a peripheral vein in a group of chronic renal failure (CRF) patients and in a group of normal patients (controls). PATIENTS: 10 CRF patients (7 males, 3 females, mean age 47 +/- 8 years old, mean body weight 66 +/- 8 kg) candidates to cadaveric renal transplantation and free from major hepatic diseases (study group); 8 ASA I patients (5 males, 3 females), without major cardiorespiratory, hepatic, renal, hematologic or metabolic diseases undergoing minor elective surgical procedures lasting from 50 to 90 minutes (control group). MEASUREMENTS: a) propofol blood concentrations by means of HPLC; b) derived pharmacokinetic parameters (calculated by means of Siphar, version 4.0, Societé de informatique médicale, Simed, Paris, 1991); c) cardiovascular parameters (heart rate, central venous pressure, invasive arterial pressure). MAIN RESULTS: The decay of propofol whole blood concentrations, distribution, redistribution and elimination half lives were similar in CRF and in control patients. On the contrary, significantly different in CRF patients were propofol blood concentrations from two to ten minutes following the induction dose (lower), the area under concentration- time curve (AUC) (smaller), the mean resident time (longer), the total body clearance (greater), the volumes of distribution at steady state and during the elimination phase (larger). The larger volumes of distribution are closely correlated with the significantly lower albumin concentrations in the uremic patients. An accelerated hepatic biotransformation is one of the possible explanations for the greater total body clearance of propofol in the uraemic patients: in fact an increased glucuronyltrasferase activity and glucuronoconjugation induced by phenols has been demonstrated in uraemia. On the other hand, large volumes of distribution are often associated with elevated total body clearance. The only significant change in the cardiovascular profile was a reduction of 17 +/- 8% of the systolic blood pressure one minute after the administration of the induction dose of propofol, whereas heart rate, arterial and central venous pressures were rather stable after intubation and at skin incision: proper vascular filling before the induction of anaesthesia has probably played a crucial role in maintaining hemodynamic stability. CONCLUSIONS: From the data gathered in this study, propofol can be considered a suitable anaesthetic agent for the induction of general anaesthesia in uraemic patients. In our opinion these data could constitute a basis for future protocols of total intravenous anaesthesia with propofol in uremic patients.

Fentanyl pre-treatment does not affect the pharmacokinetic profile of an induction dose of propofol in adults.

The initial disposition of propofol was reported to change when the administration was preceded by fentanyl. The pharmacokinetic profile of the induction dose of propofol (2 mg kg-1 body weight) was studied in 20 ASA I patients randomly allocated to receive fentanyl 1.5 microgram kg-1 (n = 12) or not (n = 8). Anaesthesia was maintained with isoflurane in N2O/O2. Venous blood drawn from the contralateral arm was used to determine whole blood propofol concentrations. The mean propofol blood concentrations were comparable in the two groups and were best fitted by a three exponential equation in all the patients, conforming to a three-compartment open mammillary model. Distributions (T1/2 alpha) redistribution (T1/2(7)) and elimination (T1/2 beta half-lives were comparable in the groups, without significant differences in the total body clearance in the area under the time-concentration curve (zero-infinity) in the volume of distribution at steady-state, in the volume of distribution during the elimination phase or in the mean resident time. Our data support the conclusion that pretreatment with fentanyl does not affect the pharmacokinetic profile of the induction dose of propofol in ASA I patients.

Changes in circulating levels of atrial natriuretic factor (ANF) during orthotopic liver transplantation in humans.

Atrial natriuretic factor (ANF) is a 28 amino acid peptide secreted by the atrial cardiocytes. Clearance is via the lung (50%) and the liver (25%). The main stimulus to ANF secretion is atrial distension but vasoconstrictors, sympathetic stimulation, catecolamines and tachycardia are able to enhance its circulating blood levels. ANF blood concentrations were measured during orthotopic liver transplantation in six postnecrotic cirrhotic patients. Significant increases in ANF blood levels occurred at the end of the anhepatic phase (P < or = 0.02 vs baseline) associated with low cardiac filling pressures (P < or = 0.02 vs baseline) and increased systemic vascular resistances (P < or = 0.02 vs preanhepatic phase). Aldosterone blood levels showed a similar behaviour, increasing significantly (P > or = 0.001 vs baseline) at the end of the anhepatic phase. ANF fell after reperfusion of the graft and returned towards baseline values at the end of the procedure. Since most of the total body clearance of ANF is performed by the lungs, its sharp increase at the end of the anhepatic phase could be considered a counterregulatory response to vasoconstricting stimulation and to fluid-sparing mechanisms in the presence of relative hypovolaemia. Its decrease after reperfusion could be related to volume normalization and partly to the enhanced clearance performed by the newly grafted liver.

Somatomedin C (IGF I) plasma levels after orthotopic liver transplantation (OLT) in end-stage cirrhotic patients.

Insulin-like growth factors [IGF I and II or somatomedins (SMS)] are polypeptides chemically and biologically correlated with insulin. The main source of synthetic activity and secretion is the liver, although many other tissues have been demonstrated to synthesize SMS. In the circulation, they are not present in a free form, but are mostly bound to a specific carrier protein independently synthesized in the liver. Hepatic or extrahepatic storage organs have not been demonstrated; the half life of the SMS-binding protein complex is between 3 and 4. Synthesis of SMS is regulated by GH, insulin, thyroxine and nutrition (caloric and protein intake, and nitrogen balance). The role of corticosteroids is still a matter of debate: in patients treated with steroids SMS blood levels have been shown to be within normal limits, while biological activity has been demonstrated to be significantly reduced by SMS inhibitors, probably induced by corticosteroid therapy. The biological properties of SMS are related to their structural homology with insulin, and can be summarized as follows: A. Insulin-like activity (glucose oxidation, lipogenesis, glycogen synthesis, inhibition of lipolysis and glycogenolysis); B. Sulphation activity (incorporation of sulphate and leucine into glycosaminglycans of the cartilage); C. Stimulation of fibroblast multiplication; D. Amplification of other hormone activities (GH); E. Complementary anabolic activity with insulin. Low levels of SMS have been demonstrated in hypopituitarism (secondary) or in other diseases independent of GH reduced secretion (primary) such as malnutrition, malabsorption, acute or chronic liver failure and uraemia. Negative nitrogen balance, hypocaloric and/or low protein diets are usually correlated with low levels of SMS. Recently, Schalch et al. reported on the role of orthotopic liver transplantation (OLT) in normalizing SMS blood levels in a group of end-stage liver diseased patients. This preliminary paper deals with changes in IGF-I plasma levels (somatomedin C) in a group of patients affected by end-stage liver cirrhosis before and after OLT.