Plasma-exchange therapy in chronic inflammatory demyelinating polyneuropathy. A double-blind, sham-controlled, cross-over study. Plasma exchange in chronic inflammatory demyelinating polyradiculoneuropathy. Beneficial effects of plasma exchange in acute inflammatory polyradiculoneuropathy. Plasma exchange in polyneuropathy associated with monoclonal gammopathy of undetermined significance. Haemodynamic optimisation improves tissue microvascular flow and oxygenation after major surgery: a randomised controlled trial. Appropriate number of plasma exchanges in Guillain-Barré syndrome. The French Cooperative Group on Plasma Exchange in Guillain-Barré Syndrome. Efficiency of plasma exchange in Guillain-Barré syndrome: role of replacement fluids. French Cooperative Group on Plasma Exchange in Guillain-Barré syndrome. A plasma exchange versus immune globulin infusion trial in chronic inflammatory demyelinating polyradiculoneuropathy. Cerebrospinal and peripheral human immunodeficiency virus type 1 load in a multisite, randomized, double-blind, placebo-controlled trial of D-Ala1-peptide T-amide for HIV-1-associated cognitive-motor impairment.
Eighteen patients with definite, untreated chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) of chronic progressive (nine patients) or relapsing course (nine patients) were randomized prospectively to receive 10 plasma-exchange (PE) or sham plasma-exchange (SPE) treatments over 4 weeks in a double-blind trial. After a wash-out period of 5 weeks or when they returned to baseline scores, patients were crossed over to the alternate treatments. Neurological function was assessed serially using a quantitative neurological disability score (NDS), a functional clinical grade (CG) and grip strength (GS) measurements. Electrophysiological studies were done at the beginning and end of each treatment. A primary 'intention to treat' analysis showed significant improvement with PE in all clinical outcome measures: NDS by 38 points, P < 0.001; CG by 1.6 points, P < 0.001; GS by +13 kg, P < 0.003 and in selected electrophysiological measurements, sigma proximal CMAP, P < 0.01; sigma motor conduction velocities, P < 0.006; sigma distal motor latencies, P < 0.01. Fifteen patients completed the trial and of those, 12 patients (80%) improved substantially with PE; i.e. five out of seven patients with chronic progressive course and seven out of eight patients with relapsing CIDP improved. There were three drop-outs; one patient lost venous access; one patient suffered a stroke and one patient left the trial to receive open treatment elsewhere. The improvement in motor functions correlated with the electrophysiological data, i.e. with improved motor conduction velocities and reversal of conduction block. Eight of 12 PE responders (66%) relapsed within 7-14 days after stopping PE. All improved with subsequent open label PE; all but two patients required long-term immunosuppressive drug therapy for stabilization. The PE non-responders improved with prednisone. We conclude that PE is a very effective adjuvant therapy for CIDP of both chronic progressive and relapsing course; concurrent immunosuppressive drug treatment is required. Exchange treatments should be given two to three times per week until improvement is established; the treatment frequency should then be tapered over several months. Plasma exchange has been reported to be efficacious in chronic inflammatory demyelinating polyradiculoneuropathy. We performed a prospective double-blind trial in which patients with static or worsening disease were randomly assigned to plasma exchange (n = 15) or to sham exchange (n = 14) for three weeks. After three weeks, we observed statistically significant differences in combined measurements of nerve conduction (total, motor, proximal, velocity, and amplitude) favoring patients who had received plasma exchange. Improvement to a greater degree than for any patient receiving sham exchange was detected in the neurologic-disability score in five patients (P = 0.025) and in subset scores for weakness and reflex in four patients (P less than 0.057). We conclude that for some patients with chronic inflammatory demyelinating polyradiculoneuropathy, plasma exchange has an ameliorating effect on neurologic dysfunction and nerve conduction, but in others no improvement is observed. Because plasma was replaced with normal serum albumin, a humoral factor or factors may have a role in the neurologic deficit of this disorder. The results of a controlled trial in which 38 patients with severe acute inflammatory polyradiculoneuropathy took part indicate that plasma exchange favourably influenced the course of the disease. Significant benefits were seen in time until onset of improvement, course of muscular weakness, improvement in disability grades over the first 2 months, and working capacity after 1 month. Cost-benefit analysis showed that the exchange treatment resulted in net financial savings. The results suggest that plasma exchange may have a role in the treatment of severe acute inflammatory polyradiculoneuropathy. Polyneuropathy associated with monoclonal gammopathy of undetermined significance (MGUS) has been treated with plasma exchange, intravenous immune globulin, and chemotherapy, but the effectiveness of these treatments remains uncertain.
                We randomly assigned 39 patients with stable or worsening neuropathy and MGUS of the IgG, IgA, or IgM type to receive either plasma exchange twice weekly for three weeks or sham plasma exchange, in a double-blind trial. The patients who initially underwent sham plasma exchange subsequently underwent plasma exchange in an open trial.
                In the double-blind trial, the average neuropathy disability score improved by 2 points from base line (from 62.5 to 60.5) in the sham-exchange group and by 12 points (from 58.3 to 46.3) in the plasma-exchange group (P = 0.06). A similar difference was observed in the weakness score, a component of the neuropathy disability score (improvement, 1 and 10 points, respectively; P = 0.07). After treatment the summed compound muscle action potentials of motor nerves were 1.2 mV lower (worse) than at base line in the sham-exchange group and 0.4 mV higher (better) in the plasma-exchange group (P = 0.07). The greater degree of improvement with plasma exchange was equal in magnitude to or greater than the difference between not being able to walk on the heels or toes and being able to perform these activities. Changes in the vibratory detection threshold, summed motor-nerve conduction velocity, and sensory-nerve action potentials did not differ significantly between the treatment groups. In the open trial, in which patients who initially underwent sham exchange were treated with plasma exchange, the neuropathy disability score (P = 0.04), weakness score (P = 0.07), and summed compound muscle action potentials (P = 0.07) improved more with plasma exchange than they had with sham exchange. In both the double-blind and the open trial, those with IgG or IgA gammopathy had a better response to plasma exchange than those with IgM gammopathy.
                Plasma exchange appears to be efficacious in neuropathy associated with MGUS, especially of the IgG or IgA type. Post-operative outcomes may be improved by the use of flow related end-points for intra-venous fluid and/or low dose inotropic therapy. The mechanisms underlying this benefit remain uncertain. The objective of this study was to assess the effects of stroke volume guided intra-venous fluid and low dose dopexamine on tissue microvascular flow and oxygenation and inflammatory markers in patients undergoing major gastrointestinal surgery.
                Randomised, controlled, single blind study of patients admitted to a university hospital critical care unit following major gastrointestinal surgery. For eight hours after surgery, intra-venous fluid therapy was guided by measurements of central venous pressure (CVP group), or stroke volume (SV group). In a third group stroke volume guided fluid therapy was combined with dopexamine (0.5 mcg/kg/min) (SV & DPX group).
                135 patients were recruited (n = 45 per group). In the SV & DPX group, increased global oxygen delivery was associated with improved sublingual (P < 0.05) and cutaneous microvascular flow (P < 0.005) (sublingual microscopy and laser Doppler flowmetry). Microvascular flow remained constant in the SV group but deteriorated in the CVP group (P < 0.05). Cutaneous tissue oxygen partial pressure (PtO2) (Clark electrode) improved only in the SV & DPX group (P < 0.001). There were no differences in serum inflammatory markers. There were no differences in overall complication rates between the groups although acute kidney injury was more frequent in the CVP group (CVP group ten patients (22%); pooled SV and SV & DPX groups seven patients (8%); P = 0.03) (post hoc analysis).
                Stroke volume guided fluid and low dose inotropic therapy was associated with improved global oxygen delivery, microvascular flow and tissue oxygenation but no differences in the inflammatory response to surgery. These observations may explain improved clinical outcomes associated with this treatment in previous trials.
                ISRCTN 94850719. Plasma exchange (PE) is the standard treatment in Guillain-Barré syndrome (GBS) patients who have lost the ability to walk. The effect of exchanges before this stage and the optimal number of exchanges for the other patients are still unknown. We randomized 556 GBS patients according to severity and number of exchanges as follows: Zero versus 2 PEs for patients who could walk-with or without aid-but not run, or who could stand up unaided (mild group); 2 versus 4 PEs for patients who could not stand up unaided (moderate group); and 4 versus 6 PEs for mechanically ventilated patients (severe group). In the mild group, 2 PEs were more effective than none for time to onset of motor recovery (median, 4 vs 8 days, respectively). In the moderate group, 4 PEs were more beneficial than 2 for time to walk with assistance (median, 20 vs 24 days) and for 1-year full muscle-strength recovery rate (64% vs 46%). Six PEs were no more beneficial than 4 in the severe cases. Patients with mild GBS on admission should receive 2 PEs. Patients with moderate and severe forms should benefit from 2 further exchanges. The goals of this multicenter controlled trial were: (1) to study the short-term effect of plasma exchange in the Guillain-Barré syndrome when applied alone within 17 days of onset of the disease; and (2) to compare two replacement fluids, diluted albumin and fresh frozen plasma (FFP) with regard to efficacy and morbidity. Two hundred twenty patients were included, 111 in the control group, 109 in the plasma exchange group, 57 of whom were assigned to receive albumin and 52 to receive fresh frozen plasma. Treatment consisted of four plasma exchanges of two plasma volumes each, initiated on the day of randomization and repeated on alternate days. Significant short-term benefits appeared in the group that received plasma exchange as demonstrated by the reduction in the proportion of patients who required assisted ventilation after randomization, and the decrease in time before beginning weaning from ventilator, time to onset of motor recovery, and time to walk with and without assistance. No statistically significant difference was found between the group that received albumin and the group that received fresh frozen plasma. Incidents during exchanges and complications related to the plasma exchange were more frequent in patients who received fresh frozen plasma. Plasma exchange is beneficial in Guillain-Barré syndrome when it is carried out early in the course of the disease. Given its risks and the lack of its clear superiority over albumin, however, we recommend that fresh frozen plasma be abandoned in the treatment of Guillain-Barré syndrome. Chronic inflammatory demyelinating polyradiculoneuropathy is a paralytic syndrome, causing considerable disability and even death. In controlled clinical trials, plasma exchange prevented or ameliorated neurological deficits, but the efficacy of immune globulin infusion remains unproved. Also unknown is whether immune globulin infusion is as effective, or more effective, than plasma exchange and what dosages and frequencies are best. In this observer-blinded study, using some objective end points not subject to bias (e.g., summated compound muscle action potential), 20 patients with progressive or static polyneuropathy were randomly assigned to receive either of the two treatments for 6 weeks, followed by a washout period, and then were assigned to receive the other treatment. Plasma exchange (twice a week for 3 weeks then once a week for 3 weeks) and immune globulin infusion (0.4 gm/kg once a week for 3 weeks, then 0.2 gm/kg once a week for the next 3 weeks) were used. End points assessed before and after treatment schedules were neurological disability score; muscle weakness of the neurological disability score; summated compound muscle action potentials of ulnar, median, and peroneal nerves; summated sensory nerve action potentials of ulnar and sural nerves; and vibratory detection threshold of the great toe using CASE IV. Observers were masked as to treatment used. Of 20 patients, 13 received both treatments whereas 4 did not worsen sufficiently to receive the second treatment--1 patient left the study during and 2 after the first treatment to receive unscheduled treatment elsewhere.(ABSTRACT TRUNCATED AT 250 WORDS) D-Ala1-peptide T-amide (DAPTA) has shown neuroprotection in vitro against gp120-induced loss of dendritic arborization and is promulgated as a CCR5 antagonist. A multisite, randomized, double-blind clinical trial of DAPTA versus placebo prior to combination antiretroviral therapy conducted with human immunodeficiency virus (HIV)-1 seropositive participants having cognitive impairment showed no overall cognitive effect, though subgroups with greater impairment and CD4 cell counts of 201 to 500 cells/mm3 at baseline showed significant improvement. The objective of this study was to examine whether intranasal administration of DAPTA at a dose of 2 mg three times per day (tid) was associated with a reduction of cerebrospinal fluid (CSF) and peripheral (plasma and serum) viral load among a subgroup of participants completing 6 months of treatment. Baseline and 6-month CSF (n = 92) and peripheral (plasma n = 33; serum n = 24) viral load were measured by the Roche Ultrasensitive assay, version 1.5, with reflexive use of the AMPLICOR assay and preservation of the blind. A DAPTA treatment indicator variable was tested using generalized linear models on change in viral load. Peripheral load (combined plasma and serum) was significantly reduced in the DAPTA-treated group. No group differences in CSF viral load were found. This retrospective study on a limited subgroup of the original trial sample indicated that DAPTA treatment may reduce peripheral viral load without concomitant CSF effects. Future studies should be undertaken to confirm the existence of this result and the CSF-periphery dissociation observed with respect to HIV-1-associated cognitive-motor impairment.
Moderate to high quality evidence from two small trials showed that plasma exchange provides significant short-term improvement in disability, clinical impairment and motor nerve conduction velocity in CIDP but rapid deterioration may occur afterwards. Adverse events related to difficulty with venous access, use of citrate and haemodynamic changes are not uncommon. More research is needed to identify agents which will prolong the beneficial action of plasma exchange.