A Phase II Safety and Efficacy Study on Prognosis of Moderate Pneumonia in Coronavirus Disease 2019 Patients With Regular Intravenous Immunoglobulin Therapy.

BACKGROUND: Currently, there is no specific drug for the treatment of coronavirus disease 2019 (COVID-19). Therapeutic benefits of intravenous immunoglobulin (IVIG) have been demonstrated in wide range of diseases. The present study is conducted to evaluate the safety and efficacy of IVIG in the treatment of COVID-19 patients with moderate pneumonia. METHODS: An open-label, multicenter, comparative, randomized study was conducted on COVID-19 patients with moderate pneumonia. One hundred eligible patients were randomized in 1:1 ratio either to receive IVIG + standard of care (SOC) or SOC. RESULTS: Duration of hospital stay was significantly shorter in the IVIG group compared with that of SOC alone (7.7 vs 17.5 days). Duration for normalization of body temperature, oxygen saturation, and mechanical ventilation were significantly shorter in IVIG compared with SOC. Percentages of patients on mechanical ventilation in 2 groups were not significantly different (24% vs 38%). Median time to reverse-transcription polymerase chain reaction negativity was significantly shorter with IVIG than SOC (7 vs 18 days). There were only mild to moderate adverse events in both groups except for 1 patient (2%), who died in SOC. CONCLUSIONS: Intravenous immunoglobulin was safe and efficacious as an adjuvant with other antiviral drugs in the treatment of COVID-19.

A comparative analysis of enflurane anesthesia on primate motor and somatosensory evoked potentials.

The effect of increasing enflurane concentration on magnetic-induced myogenic cranial (Cr) and peripheral (Pr) motor evoked potentials (MEPs), and electrically induced median (MN) and posterior tibial (PTN) somatosensory evoked potentials (SEPs) was studied in 10 monkeys. MEP, recorded from abductor pollicis brevis and abductor hallucis muscles, and SEP (short- and long-latency scalp recorded potentials) variables were examined at 0.25, 0.5, 0.75, 1.0 MAC enflurane concentrations. Cr-MEPs progressively attenuated (P less than 0.01) with 0.25 MAC and were abolished (greater than or equal to 0.75 MAC) by graded enflurane concentration. Stimulation threshold for Cr-MEP was progressively elevated (P less than 0.01), and eventually reliable responses were lost (greater than or equal to 0.75 MAC). Marked scalp zone reduction to obtain Cr-MEP responses was noted with increasing enflurane concentration. Pr-MEPs and most SEP peaks maintained good replicability but showed significant amplitude reduction (P less than 0.01). MEP and SEP latency values were not significantly delayed as long as the wave form remained identifiable. We conclude that enflurane has a differential influence on Cr-MEPs and SEPs. Administration of enflurane should be discouraged while monitoring myogenic Cr-MEPs since even a subanesthetic concentration is profoundly detrimental.

The effect of neuroleptanalgesia (droperiodol-fentanyl) on motor potentials evoked by transcranial magnetic stimulation in the monkey.

Motor evoked potentials (MEPs) after transcranial magnetic stimulation (TMS) have been examined in 12 monkeys under neuroleptanalgesia (NLA). Compound muscle action potentials were recorded from abductor policis brevis (APB) and gastroncnemius (GN) muscles contralateral to the stimulation site. After obtaining baseline tracings during emergence from methohexitone, 10 mg/kg i.m., NLA was induced using droperiodol, 0.3 mg/kg i.v. followed by fentanyl, 0.006 mg/kg i.v. Sequential MEP recordings were obtained 10 min after i.v. droperiodol, 2, 8, and 16 min after i.v. fentanyl, and during recovery. Replicable TMS MEPs were consistently recorded under NLA. However, droperidol and fentanyl caused significant stimulation threshold elevation, amplitude depression, and latency delay compared to control values (p <0.01). Ten minutes after droperiodol administration, the APB-GN threshold, amplitude, and latency values (mean +/- SD) were 0.81 +/- 0.2-0.84 +/- 0.1 T (baseline 0.57 +/- 0.1-0.59 +/- 0.1 T), 3.4 +/- 2.1-4.0 +/- 2.5 mV (baseline 8.0 +/- 3.7-9.0 +/- 3.7 mV), and 15.8 +/- 1.3-21.1 +/- 1.2 ms (baseline 14.9 +/- 1.2-20.1 +/- 1.3 ms), respectively. Addition of fentanyl resulted in further response deterioration. Two minutes after fentanyl injection, the APB-GN threshold, amplitude, and latency values were 0.88 +/- 0.18-0.95 %% 0.15 T, 2.1 +/- 1.7-2.0 +/- 2.1 mV, and 16.0 +/- 1.4-21.9 +/- 1.3 ms, respectively. Subsequent MEPs revealed gradual response improvement but, in contrast to baseline, remained markedly altered (p <0.05). During the recovery period (53 +/- 6 min), the APB-GN threshold, amplitude, and latency measurements were 0.66 +/- 0.1-0.77 +/- 0.2 T, 4.4 +/- 3.1-4.2 +/- 2.9 mV, 15.5 %% 1.4-20.9 +/- 1.7 ms, respectively. We conclude that, in a primate model, NLA maintains measurable TMS MEPs. Nevertheless, droperiodol and fentanyl produce significant and prolonged response alterations. Knowledge of these changes, while administering NLA drugs intraoperatively, is essential to interpretation of MEP data.

The effect of an anesthetic induction dose of midazolam on motor potentials evoked by transcranial magnetic stimulation in the monkey.

The effect of a hypnotic dose (0.5 mg/kg) of midazolam (MDZ) on motor evoked potentials (MEPs) was examined in 12 monkeys. MEPs were elicited by transcranial magnetic stimulation (TMS) and the resultant potentials recorded from abductor pollicis brevis (APB) and anterior tibialis (AT) muscles contralateral to the stimulation site. After administration of MDZ, sequential MEP recordings were obtained at postinduction, hypnosis, awakening, emergence, and recovery periods. The results were compared with control values using one-way analysis of variance and Tukey's post-hoc test. Under hypnosis, MEP reproducibility was problematic as the potentials were occasionally ill identified and questionable. MDZ resulted in marked MEP scalp field reduction, coil demography alteration, stimulation threshold elevation, and amplitude suppression (p <0.01). Latency response was unaltered. During hypnosis, awakening, and recovery periods, the mean APB and AT thresholds were elevated by 39, 23, and 0% and by 60, 34, and 4% respectively; while APB and AT amplitudes were depressed by 95, 86, and 53% and by 99, 91, and 60%, respectively. We conclude that an induction dose of MDZ can produce profound and prolonged attenuation of TMS MEPs. The drug inhibitory effect on MEPs may persist after recovery. Anesthetic doses of MDZ should cautiously be used in the settings of MEP monitoring.

PAF metabolism in resident and activated alveolar macrophages: role of protein kinase C.

Platelet-activating factor (PAF) metabolism was studied in resident and activated alveolar macrophages. Macrophages were obtained from normal Sprague-Dawley rats and from rats previously injected with complete Freund's adjuvant. Macrophages were attached and stimulated for 90 min. Then, cell PAF was extracted and quantitated by thin-layer chromatography. We found that in both resident and activated macrophages, calcium ionophore A23187 was a potent stimulus for PAF production while phorbol myristate acetate (PMA) was not. PMA and ionophore acted synergistically to increase PAF content in resident macrophages. This synergism was not observed in activated macrophages. To examine if this difference between resident and activated macrophages was due to a difference in PAF degradation, we assayed acetylhydrolase, the PAF-degrading enzyme. We found that ionophore stimulated acetylhydrolase activity in activated macrophages, but not in resident macrophages. Furthermore, PMA potentiated the ionophore effect in activated macrophages. This synergism was less obvious in resident cells. We conclude that PAF metabolism is different in activated and resident alveolar macrophages. Protein kinase C may play an important role in acetylhydrolase regulation in these cells.

The effect of nitrous oxide on transcranial magnetic-induced electromyographic responses in the monkey.

Transcranial magnetic stimulation (TMS) to produce motor evoked potentials (MEPs) is a newly developed intraoperative modality to monitor functional integrity of the motor pathways. The present study was designed to examine the reliability of magnetic MEP recording under nitrous oxide (N2O) inhalation. Following ketamine injection (10 mg/kg i.m.) and endotracheal intubation, 16 monkeys were exposed to N2O:O2 mixture ratios 1:3, 1:1, and 3:1. Electromyographic (EMG) responses, evoked by pulsed magnetic fields applied extracranially to the scalp zone overlying motor cortex, were recorded from the contralateral fore- and hind limb flexor muscles. The scalp topography zone for contralateral muscle excitation was markedly reduced by 75 vol% N2O. Significant stimulation threshold elevation, latency prolongation, and amplitude depression were noted after inhalation of 75 vol% N2O (p <0.05) compared with

Intravenous albumin administration for prevention of spinal hypotension during cesarean section.

Five percent albumin in Ringer's lactate with 5% dextrose solution (D5RL) (15 ml/kg) was prophylactically infused preanesthetically over 15 to 20 minutes to prevent hypotension during spinal anesthesia in 46 patients undergoing elective cesarean section. Apgar scores and the incidence and severity of hypotension were compared to results obtained in 41 patients who were given D5RL solution without albumin (15 ml/kg). The incidence of hypotension was significantly less in patients given 5% albumin than in patients hydrated with D5RL alone. Mean arterial pressure decreased up to 18 torr from control values in patients hydrated with D5RL but mean arterial pressure did not change significantly in patients given 5% albumin. The Apgar scores, both at 1 minute and 5 minutes, were significantly higher (p < 0.01) in infants born of mothers given albumin than in infants whose mothers were given D5RL solution. Prophylactic administration of 5% albumin in D5RL solution is an effective method for prevention of spinal hypotension.