Efficacy and Safety of Intravenous Pamidronate for Parathyroid Hormone-dependent Hypercalcemia in Hospitalized Patients.

CONTEXT: Bisphosphonates are effective for hypercalcemia of malignancy (HOM). Efficacy and safety data for bisphosphonates in parathyroid hormone-related hypercalcemia (PTHRH) are rare, including pamidronate (Pam), which is not indicated for this condition. OBJECTIVE: This work aims to evaluate the efficacy and safety of Pam for moderate-to-severe PTHRH. METHODS: This retrospective case-control study was conducted at a tertiary care medical center. Patients included adults hospitalized with serum calcium levels greater than 12 mg/dL, from October 29, 2013 to December 17, 2019. Etiology was categorized as PTHRH or PTH-independent. Clinical and laboratory data of PTHRH patients treated with Pam (PTHRH-Pam+) were compared to Pam-untreated counterparts (PTHRH-Pam-). RESULTS: Thirty-four patients with 37 hospitalizations for PTHRH (Pam-treated and -untreated) met the inclusion criteria. Pam was given in 24 of 37 cases (64.8%). Admission serum calcium levels for the PTHRH-Pam+ group were higher than for PTHRH-Pam- group (14.4 mg/dL vs 13.0 mg/dL, P = .005). Median total Pam dose was 60 mg (range, 30-180 mg) in the treated group. Serum calcium decreased 3.5 mg/dL for PTHRH-Pam+ vs 1.6 mg/dL for PTHRH-Pam- (P = .003). No PTHRH-Pam+ patients developed hypocalcemia or acute kidney injury. Nadir serum phosphorus levels were lower in the PTHRH-Pam+ vs PTHRH-Pam- group (1.7 mg/dL vs 2.4 mg/dL, respectively, P = .004). Three PTHRH-Pam+ patients developed severe hypophosphatemia; all resolved with intravenous and oral supplementation. Seventeen patients underwent parathyroidectomy, of whom 10 received Pam within 28 days preoperatively. Postoperatively, 4 developed hypocalcemia and 3 hypophosphatemia. CONCLUSION: This study demonstrates that Pam is effective and safe for treating PTHRH, while ensuring close laboratory monitoring of calcium and phosphorus metabolism. Larger, prospective studies are needed to establish the role of Pam and other potent bisphosphonates in moderate-to-severe PTHRH.

Structured, Protocol-Based Pulse-Oximetry Measurement Improves the Evaluation of Hypoxemic Patients at Hospital Admission.

BACKGROUND: Accurate pulse oximetry reading at hospital admission is of utmost importance, mainly for patients presenting with hypoxemia. Nevertheless, there is no accepted or evidence-based protocol for such structured measuring. OBJECTIVES: To devise and assess a structured protocol intended to increase the accuracy of pulse oximetry measurement at hospital admission. METHODS: The authors performed a prospective comparison of protocol-based pulse-oximetry measurement with non-protocol based readings in consecutive patients at hospital admission. They also calculated the relative percentage of improvement for each patient (before and after protocol implementation) as a fraction of the change in peripheral capillary oxygen saturation (SpO2) from 100%. RESULTS: A total of 460 patients were recruited during a 6 month period. Implementation of a structured measurement protocol significantly changed saturation values. The SpO2 values of 24.7% of all study participants increased after protocol implementation (ranging from 1% to 21% increase in SpO2 values). Among hypoxemic patients (initial SpO2 < 90%), protocol implementation had a greater impact on final SpO2 measurements, increasing their median SpO2 readings by 4% (3-8% interquartile range; P < 0.05). Among this study population, 50% of the cohort improved by 17% of their overall potential and 25% improved by 50% of their overall improvement potential. As for patients presenting with hypoxemia, the median improvement was 31% of their overall SpO2 potential. CONCLUSIONS: Structured, protocol based pulse-oximetry may improve measurement accuracy and reliability. The authors suggest that implementation of such protocols may improve the management of hypoxemic patients.

Is rivastigmine safe as pretreatment against nerve agents poisoning? A pharmacological, physiological and cognitive assessment in healthy young adult volunteers.

Rivastigmine, a reversible cholinesterase inhibitor, approved as a remedy in Alzheimer's disease, was suggested as pretreatment against nerve agents poisoning. We evaluated the pharmacokinetic, pharmacodynamic, physiologic, cognitive and emotional effects of repeated rivastigmine in young healthy male adults, in a double blind, placebo controlled crossover trial. Three groups completed 3 treatment periods: 0, 1.5 and 3mg twice a day, for a total of 5 intakes. Parameters monitored were: vital signs, ECG, laboratory tests, sialometry, visual accommodation, inspiratory peak flow, and cognitive function tests. Adverse reactions were mild. Peak blood levels and peak cholinesterase inhibition increased with repeated intakes, and high variability and non-linear pharmacokinetics were demonstrated. In addition, two cognitive functions were affected (perceptual speed and dynamic tracking). The complicated pharmacological profile and the high inter-personal variability limit the potential use of rivastigmine as pretreatment for war fighters and first responders.

Airway control in case of a mass toxicological event: superiority of second-generation supraglottic airway devices.

INTRODUCTION: Early respiratory support and airway (AW) control with endotracheal intubation (ETI) are crucial in mass toxicology events and must be performed while wearing chemical personal protective equipment (C-PPE). AIM: The aim of this study is to evaluate the efficiency of AW control by using second-generation supraglottic AW devices (SADs) as compared with ETI and first-generation SAD while wearing C-PPE. METHODS: This is a randomized crossover trial involving 117 medical practitioners. Four AW management devices were examined: endotracheal tube, the first-generation SAD, laryngeal mask AW unique and 2 second-generation SAD, the laryngeal tube suction disposable, and supreme laryngeal mask AW (SLMA). Primary end point measured were success or failure, number of attempts, and time needed to achieve successful device insertion. Secondary end point was a subjective appraisal of the AW devices by study population. RESULTS: More attempts were required to achieve AW control with endotracheal tube, with and without C-PPE (P<.001). Time to achieve AW control with ETI was, on average, 88% longer than required with other devices and improved with practice. The mean times to achieve an AW were longer when operators were equipped with C-PPE as compared with standard clothing. Subjectively, difficulty levels were significantly higher for ETI than for all other devices (P<.0001). CONCLUSIONS: When compared with ETI, the use of SADs significantly shortened the time for AW control while wearing C-PPE. Second-generation SAD were superior to laryngeal mask AW unique. These finding suggest that SADs may be used in a mass toxicology event as a bridge, until definite AW control is achieved.

Prevention of organophosphate-induced chronic epilepsy by early benzodiazepine treatment.

Poisoning with organophosphates (OPs) may induce status epilepticus (SE), leading to severe brain damage. Our objectives were to investigate whether OP-induced SE leads to the emergence of spontaneous recurrent seizures (SRSs), the hallmark of chronic epilepsy, and if so, to assess the efficacy of benzodiazepine therapy following SE onset in preventing the epileptogenesis. We also explored early changes in hippocampal pyramidal cells excitability in this model. Adult rats were poisoned with the paraoxon (450µg/kg) and immediately treated with atropine (3mg/kg) and obidoxime (20mg/kg) to reduce acute mortality due to peripheral acetylcholinesterase inhibition. Electrical brain activity was assessed for two weeks during weeks 4-6 after poisoning using telemetric electrocorticographic intracranial recordings. All OP-poisoned animals developed SE, which could be suppressed by midazolam. Most (88%) rats which were not treated with midazolam developed SRSs, indicating that they have become chronically epileptic. Application of midazolam 1min following SE onset had a significant antiepileptogenic effect (only 11% of the rats became epileptic; p=0.001 compared to non-midazolam-treated rats). Applying midazolam 30min after SE onset did not significantly prevent chronic epilepsy. The electrophysiological properties of CA1 pyramidal cells, assessed electrophysiologically in hippocampal slices, were not altered by OP-induced SE. Thus we show for the first time that a single episode of OP-induced SE in rats leads to the acquisition of chronic epilepsy, and that this epileptogenic outcome can be largely prevented by immediate, but not delayed, administration of midazolam. Extrapolating these results to humans would suggest that midazolam should be provided together with atropine and an oxime in the immediate pharmacological treatment of OP poisoning.

Using MRI for the assessment of paraoxon-induced brain damage and efficacy of antidotal treatment.

Organophosphate intoxication induces neural toxicity as demonstrated in histological analysis of poisoned animals. Diffusion-weighted magnetic resonance imaging (DWMRI) enables early noninvasive characterization of biological tissues based on their water diffusion characteristics. Our objectives were to study the application of MRI for assessment of paraoxon-induced brain damage and the efficacy of antidotal treatments. Seventy-six rats were poisoned with paraoxon followed by treatment with atropine and obidoxime. The rats were then divided into five treatment groups consisting of midazolam after 1 or 30 min, scopolamine after 1 or 30 min and a no anticonvulsant treatment group. Five untreated rats served as controls. Animals underwent MRI on days 1, 8, 15, 29 and 50 post poisoning. Histological evaluation was performed on representative rat brains. Acute DWMRI effects, such as enhancement of temporal brain regions, and chronic effects such as ventricular enlargement and brain atrophy, depicted on T2-weighted MRI, were significantly more prominent in late anticonvulsant treatment groups. There was no significant difference between the neuroprotective effects of midazolam and scopolamine as shown by DWMRI. Early MRI abnormalities were found to correlate significantly with histological analysis of samples obtained 15 days post treatment. In conclusion, our results demonstrate the feasibility of using DWMRI for depiction of early cytotoxic response to paraoxon and T2-weighted MRI for later changes, thus enabling assessment of early/late brain damage as well as treatment efficacy in rats. The ability to depict these changes early and noninvasively may be applied clinically in the acute phase of organophosphate poisoning.

The effects of general vs spinal anesthesia on frontal cerebral oxygen saturation in geriatric patients undergoing emergency surgical fixation of the neck of femur.

STUDY OBJECTIVE: To assess the effect of regional vs general anesthesia on transcranial cerebral oxygen saturation (rSo2). DESIGN: Prospective, randomized, open-label study. SETTING: Large referral hospital. PATIENTS: Sixty American Society of Anesthesiologists physical status I, II, and III geriatric patients at least 60 years of age, undergoing surgical fixation of the neck of femur. INTERVENTIONS: Patients were randomized to receive either general (group GA) or spinal (group S) anesthesia. In all cases, frontal rSo2 was measured for a 10-minute preoperative control period, throughout the surgical procedure, and for 10 minutes postoperatively. MEASUREMENT AND MAIN RESULTS: The frequency of a decrease in rSo2 below baseline preoperative levels was significantly (P < .0001) higher in group S. However, the number of patients in whom at least one dip below baseline was recorded was similar between the groups. By contrast, general anesthesia was associated with a significantly higher rSo2 when compared with spinal anesthesia. Logistic regression revealed no correlation between changes in blood pressure, heart rate, or peripheral oxygen saturation and the frequency of rSo2 dips below baseline. CONCLUSION: Cerebral oxygen saturation is likely patient specific and independent of the anesthetic technique administered. Spinal anesthesia is associated with a higher incidence of cerebral desaturation. However, the number of patients in whom at least one dip below baseline was recorded was similar between the groups.