Mode of inhalation for trained and untrained asthmatics using a pressurized aerosol

A pressurized inhalation aerosol should be actuated at the beginning of a slow and deep inhalation, followed by a long pause of breathholding. In this study a registration was performed on the mode of inhalation. The flow-volume curve and the moment of actuation were obtained from an aerosol actuator provided with sensors, and the breathholding pause was measured. Data were obtained from 34 asthmatic patients, regularly trained to use the pressurized aerosol, and these data were compared with those from 44 untrained patients. When the subjects used a terbutaline sulfate aerosol in their usual fashion, most of the trained subjects succeeded well. Further improvements could possibly be made regarding the depth of inhalation and, after control with the recording device, regarding the flow rate at actuation. Most of the untrained subjects did not use a deep enough inhalation with respect to their vital capacity, and their breath-holding pause was very short. It only seems possible to improve these parameters by regular training. In order to reach optimal results the asthmatic patients must be regularly controlled and instructed regarding their use of a pressurized inhalation aerosol. A recording device is useful in demonstrating to each subject which parameter can be improved.     

Dose-response characteristics of nebulized albuterol in the treatment of acutely ill, hospitalized asthmatics.

We investigated the bronchodilator dose-response to nebulized albuterol and the dose of albuterol which produces maximal bronchodilation in the acutely ill, hospitalized asthmatic. Consecutively admitted patients from the emergency room in status asthmaticus who fulfilled the inclusion criteria (age <41 years old and <12 pack-years of smoking) were studied. Albuterol was administered by nebulizer (Puritan-Bennett Raindrop) in repeated 2.5-mg treatments up to a total dose of 10 mg and the bronchodilator response was measured by a computerized spirometer. Twenty-two patients were studied. Baseline spirometry showed a (mean +/- SE) forced expiratory volume in 1 sec (FEV1) of 1.26 +/- 0.14 L (42 +/- 4.0% predicted), which increased significantly (p < 0.05) during albuterol titration to a maximum FEV1 of 1.70 +/- 0.19 L (57 +/- 5% of predicted). After cumulative doses of 2.5, 5.0, 7.5, and 10.0 mg of nebulized albuterol, 27%, 45%, 72%, and 77% of patients, respectively, attained maximum bronchodilation. The remaining 23% of patients did not respond to doses up to 10 mg of albuterol. The maximum FEV1 response to albuterol did not correlate with the initial severity of airflow obstruction (r = 0.36, p > 0.05). Pulse rate and arterial oxygen saturation were not significantly affected by nebulized albuterol up to a total dose of 10 mg. No arrhythmias were noted. In summary, most hospitalized asthmatics (72%) required a cumulative dose of 7.5 mg of nebulized albuterol to achieve maximum bronchodilation and a large fraction (50%) required higher albuterol doses than the standard 2.5 mg. The bronchodilatory response to nebulized albuterol varied widely among patients in status asthmaticus and could not be predicted from the initial severity of airflow obstruction. Because side effects were minimal, it would be reasonable to use 7.5 mg of nebulized albuterol as initial therapy. Alternatively, dose-response titration with albuterol would be advantageous.     

A protocol for improved glycaemic control following corticosteroid therapy in diabetic pregnancies.

AIMS: Diabetic pregnancies have an increased risk of respiratory distress syndrome (RDS) and preterm delivery. Antenatal corticosteroids can prevent RDS but induce acute severe hyperglycaemia. We have developed a protocol which prevents hyperglycaemia and can be used easily by ward staff. METHODS: Intramuscular dexamethasone is given in two doses 12 h apart. Subcutaneous insulin and diet are continued but from the first dexamethasone dose until 12 h after the second, supplementary intravenous insulin is infused according to hourly blood glucose measurements. The protocol incorporates four graded sliding scales. The initial scale is selected according to the patient's current subcutaneous insulin dose and advanced if the blood glucose is > or = 10.1 mmol/l for 2 consecutive hours. RESULTS: In a 10-month period eight (three gestational, five pre-gestational) women received antenatal corticosteroids from a total of 37 diabetic pregnancies. The median amount of supplementary intravenous insulin required was 74 U (range 32-88 U); the median glucose values achieved were 5.8-8.9 mmol/l. Seventy-five percent of glucose measurements were within an acceptable range of 4-10 mmol/l. Only one baby developed RDS. DISCUSSION: Large amounts of supplementary intravenous insulin are needed to achieve even moderate glycaemic control. This protocol enables routine ward staff to manage this successfully.     

Pulse oximetry for tapering supplemental oxygen in hospitalized patients. Evaluation of a protocol

In a randomized study, we determined the clinical and financial effects of replacing arterial blood gas measurements with finger pulse oximeter readings during the process of tapering supplemental oxygen in hospitalized patients. The 16 patients in the control group, whose management followed conventional practice in our hospital, received a total of 57 arterial blood gas measurements during the 6.6 (mean) days it took for them to taper to their discharge supplemental oxygen level (usually room air). The 13 patients randomized to the oximeter study group had their arterial oxygen saturation monitored by pulse oximetry. The physicians of patients in the oximeter group were at liberty to obtain arterial blood gas determinations during the study if they desired. The oximeter study group had fewer (p less than 0.005) arterial punctures for blood gas measurements (total of 16 for the group) and fewer (p less than 0.001) days on supplemental oxygen (mean of 2.7 days per patient). We conclude that substituting noninvasive pulse oximetry for arterial blood gas measurements during reductions of supplemental oxygen shortened the days of oxygen use and decreased the number of arterial blood gas determinations in our patients. In addition to reducing the discomfort to patients, the use of oximetry was of financial benefit in that it reduced medical personnel time, blood gas analyzer use, and duration of oxygen administration.     

Hypothermia therapy for the treatment of acute myocardial infarction: A protocol for systematic review and meta-analysis

Background:In patients with acute myocardial infarction (AMI) receiving percutaneous coronary intervention (PCI), the role of systemic therapeutic hypothermia remains controversial. We performed a protocol for systematic review and meta-analysis to investigate the effect of systemic therapeutic hypothermia in patients with AMI receiving PCI.Methods:This study will use the Cochrane Library, Web of Science, PubMed, Embase, Allied and Complementary Medicine Database, China Biomedical Literature Database, China National Knowledge Infrastructure, China Science and Technology Journal Database, Wanfang Database, and Ongoing Clinical Trials Database. The search terms were hypothermia, cooling, myocardial infarction, myocardial ischemia and acute coronary syndrome. Quality assessment of the included studies was evaluated using the Cochrane risk of bias assessment tool. Statistical analyses were performed using RevMan 5.4 software.Results:The findings of this study will be submitted to peer-reviewed journals for publication.Conclusion:This systematic review will provide evidence to determine whether hypothermia therapy is an effective and safe intervention for patients with AMI receiving PCI.Registration number: 10.17605/OSF.IO/9XJSB.     

Asthma therapy modulates priming-associated blood eosinophil responsiveness in allergic asthmatics.

Eosinophils play an important role in the pathogenesis of asthma. Several pro-inflammatory responses of eosinophils are primed in vivo in this disease. The aim of the present study was to investigate whether regular antiasthma treatment could modulate priming-sensitive cytotoxic mechanisms of human eosinophils. In a randomized, two-centre, double-blind parallel group study, the effect of 8 weeks of treatment with salmeterol xinafoate 50 microg b.i.d., beclomethasone dipropionate 400 microg b.i.d. or both on pulmonary function and the activation of priming-sensitive cytotoxic mechanisms of eosinophils, i.e. degranulation of eosinophil cationic protein (ECP) in serum, and activation of isolated eosinophils in the context of induction of the respiratory burst and release of platelet-activating factor (PAF) were tested. These effects were evaluated in 40 allergic asthmatics before and 24 h after allergen inhalation challenge. Whereas baseline forced expiratory volume in one second (FEV1) improved in all treatment groups, only treatment with a combination of salmeterol and beclomethasone significantly inhibited the allergen-induced increase in serum ECP, and (primed/unprimed) PAF-release, suggesting inhibition of eosinophil priming after allergen challenge. In contrast to the combination therapy, monotherapy with beclomethasone had no influence on allergen-induced PAF-release, suggesting an additional anti-inflammatory effect of salmeterol during combination therapy. Monotherapy with beclomethasone inhibited the prechallenge serum-treated zymosan (STZ) (0.1 mg mL(-1))-induced respiratory burst and the allergen-induced increase in serum ECP levels, reflecting pre- and postchallenge anti-inflammatory effects. During monotherapy with salmeterol, an allergen-induced increase in serum ECP concentration and STZ (0.1 mg x mL(-1))-induced respiratory burst was observed, suggesting that treatment with salmeterol alone had no effect on priming-sensitive eosinophil cytotoxic mechanisms. In conclusion, this study shows that standard asthma therapy leads to inhibition of eosinophil priming of cytotoxic mechanisms in vivo.     

Efficacy and safety of pricking-blood therapy for acute gouty arthritis: A protocol for systematic review and meta-analysis

Background:Acute gouty arthritis is a joint inflammatory reaction that affects the daily quality of patients. Previous reviews of pricking-blood therapy for acute gouty arthritis have been growing, but a systematic review is not available. This study aimed to systematically investigate the efficacy and safety of pricking-blood therapy in treating acute gout arthritis.Methods:We will search for relevant literature through Chinese and English databases, with the retrieval deadline being December 2020. Databases include PubMed, Embase, Web of Science, the Cochrane Library, China National Knowledge Infrastructure, the Chongqing VIP Chinese Science and Technology Periodical Database, Wanfang Database, and China Biomedical Literature Database. We will also manually search Chinese Acupuncture & Moxibustion, Acupuncture Research, Chinese Clinical Trial Register, and unpublished studies or references. According to the inclusion and exclusion criteria, the literature will be screened, and the data are extracted independently by the 2 researchers. The primary outcomes were the total effective rate and Visual Analogue Scale (VAS) score. RevMan 5.3.5. software will be used for statistical analysis. According to the Grades of Recommendation, Assessment, Development, and Evaluation (GRADE), each evidence of outcome quality will be appraised.Results:This study will provide a comprehensive review of current evidence for a pricking-blood therapy treatment for acute gouty arthritis.Conclusion:The efficacy and safety of picking-blood therapy in treating acute gout arthritis will be evaluated.Unique INPLASY number:INPLASY2020100094.     

Plasma concentrations of salbutamol in acute severe asthmatics

We studied prospectively 11 asthmatic patients presenting to the Accident and Emergency department with acute asthma. (Four patients reported historically that they were taking some form of oral salbutamol as part of their maintenance therapy.) Standard cardiovascular and respiratory parameters and plasma salbutamol concentrations were measured before and one hour after treatment with five milligrams of nebulised salbutamol. The median plasma salbutamol concentration before treatment was below the level of detection of the assay (less than 3 ug.l^-1) with a range from less than 3 ug.l^-1 to 34.6 ug.l^-1. One hour post treatment the median plasma salbutamol concentration was 7.4 ug.l^-1 (range<3.0 ug.1^-1 to 56.0 ug.1^-1) p <0.05. (Wilcoxons test). Correlations were investigated between the measured pretreatment physiological variables and pre-treatment plasma salbutamol concentrations. None were found to be significant. Similar analysis of the measured post-treatment physiological variables and post-treatment plasma salbutamol concentrations again revealed no significant correlations. However, a significant negative correlation was noted between the change in plasma salbutamol concentration with treatment and the change in respiratory rate (Rs=–0.56, p= 0.04). If asthmatics do indeed use high doses of inhaled beta-2-agonists (salbutamol) in an attempt to abort an acute attack (as many clinicians suspect) little, if any, of the drug appears to reach the systemic circulation. In this study the administration of five milligrams of nebulised salbutamol to acute asthmatics did not produce excessive increases in plasma salbutamol concentration, even in those patients taking oral salbutamol as part of their maintenance therapy.     

Statin therapy may protect against acute kidney injury in patients hospitalized for interstitial SARS-CoV2 pneumonia

Background and aimsCOVID-19-associated acute kidney injury (AKI) represents an independent risk factor for all-cause in-hospital death in patients with COVID-19. Chronic statin therapy use is highly prevalent in individuals at risk for severe COVID-19. Our aim is to assess whether patients under treatment with statins have a lower risk of AKI and in-hospital mortality during hospitalization for interstitial SARS-CoV2 pneumonia.Methods and resultsOur study is a prospective observational study on 269 consecutive patients admitted for COVID-19 pneumonia at the Internal Medicine Unit of IRCCS Sant'Orsola Hospital in Bologna, Italy. We compared the clinical characteristics between patients receiving statin therapy (n = 65) and patients not treated with statins and we assessed if chronic statin use was associated with a reduced risk for AKI, all-cause mortality, admission to ICU, and disease severity. Statin use was associated with a significant reduction in the risk of developing AKI (OR 0.47, IC 0.23 to 0.95, p 0.036) after adjustment for age, sex, BMI, hypertension, diabetes, and chronic kidney disease (CKD). Additionally, statin use was associated with reduced C-reactive protein (CRP) levels (p 0.048) at hospital admission. No significant impact in risk of all-cause mortality (HR 1.98, IC 0.71 to 5.50, p 0.191) and ICU admission (HR 0.93, IC 0.52 to 1.65, p 0.801) was observed with statin use, after adjustment for age, sex, BMI, hypertension, diabetes, and CKD.ConclusionThe present study shows a potential beneficial effect of statins in COVID-19-associated AKI. Furthermore, patients treated with statins before hospital admission for COVID-19 may have lower systemic inflammation levels.     

A model for conversion from small volume nebulizer to metered dose inhaler aerosol therapy.

Rationing of medical services will be necessary if we do not develop a more rational and efficient health care system. Respiratory care services are receiving emphasis as we try to curtail spiraling health care costs. In analysis of our respiratory care services, we found that small volume nebulizer (SVN) therapy was still a major portion of our workload. We instituted a protocol to convert to metered dose inhaler (MDI) therapy. All hospitalized patients, excluding those admitted to the spinal cord unit and intensive care units, with a physician's order for aerosol delivery by SVN, were evaluated by respiratory care practitioners for conversion to MDI therapy. A simple protocol for the therapist to use in this conversion was developed. All patients converted to MDI were trained in appropriate MDI use by the therapist. A three-day follow-up of each patient's compliance with proper MDI therapy was initiated. Even with a 72-h allowance for initial SVN treatment, we realized a 9,350 procedure reduction from deleted treatments and an additional 7,650 conversions to MDI. Less than 2 percent of our patients failed to make a completely successful conversion to MDI. Those patients who successfully converted to MDI resulted in reduced hospital costs of $43,758 based on excess medication, supplies, and labor costs associated with SVN treatments. We also saved 5,000 h of technician time that was used to further instruct patients in appropriate MDI therapy. Aerosol therapy by MDI is cost-effective therapy. The institution of guidelines for MDI conversion has reduced fear of failure for both clinicians and patients and illustrates the importance of patient education by qualified respiratory therapists.     

Quinidine therapy in hospitalized patients with ventricular arrhythmias.

Quinidine serum levels and pharmacokinetic data were assessed during steady state therapy with oral quinidine sulfate in 19 hospitalized patients who were being treated for ventricular arrhythmias. A new high performance liquid chromatography assay was employed. Four patients were studied both after the first dose of quinidine and at steady state, and the initial dose pharmacokinetic values were found not to be predictive of steady state. The mean half-life of quinidine was 4.5 hours, but there was wide individual variation. The elimination rate constant for quinidine was significantly lower in patients with echocardiographic evidence of left ventricular dilatation than in patients with normal echocardiographic left ventricular size. The average urinary excretion of quinidine was only 11.3%. The pharmacokinetic data in seven chronic alcoholic patients without clinical or laboratory evidence of hepatic insufficiency did not differ from the data obtained in nonalcoholic patients. However, with severely impaired liver function, there may be marked prolongation of quinidine half-life predisposing to quinidine toxicity. The possible clinical implications of these findings are discussed.     

Cost-benefit comparison of aerosol bronchodilator delivery methods in hospitalized patients

We compared two modes of aerosol bronchodilator delivery in 34 patients hospitalized with obstructive airways diseases. The standard mode, therapist-administered up-draft nebulization (UDN), is labor-intensive and therefore relatively costly. The alternative mode, self-administration by a metered dose inhaler (MDI), is less costly, but its efficacy over an entire hospitalization has heretofore not been established. Patients were enrolled after transfer to the pulmonary ward from the emergency room or intensive care units (ICU). We then randomized them to receive metaproterenol q4h either via MDI or UDN. Daily spirometry revealed that MDI and UDN were associated with equivalent bronchodilation initially and equivalent improvement at discharge. The duration of hospitalization for the two groups was also the same. Thus, the two delivery methods were equally effective. We could not attribute this equivalence to pretreatment intergroup differences or to differences in concomitant therapy with steroids, theophylline, other bronchodilators, or antibiotics. Routine use of MDI rather than UDN in all non-ICU adult patients would save $253,487 per year at our institution alone.     

Future directions in aerosol therapy

An unprecedented growth in new technology and clinical applications of aerosol therapy is forecast for the new millennium. The most promising areas of investigation in the aerosol field relate to improvements in the pulmonary deposition of aerosol, improved synchronization between the patient's breathing and aerosol generation, targeting of aerosol to specific sites in the lung, improvements in the formulations of inhaled drugs, modulated release of inhaled drugs, and use of inhaled drugs for systemic therapy. Moreover, gene therapy by the inhaled route offers the prospects of a cure for a variety of pulmonary disorders. Future developments in the aerosol field are expected to radically change the management of patients across several medical specialties.     

Hematin therapy for acute porphyria.

1. A therapeutic trial of intravenous hematin is presented. Eleven cases of AIP and one of VP who did not improve with conventional treatment (high carbohydrate intake) received this new agent. 2. Urinary ALA, PBG and, when possible, uroporphyrin and coproporphyrin were used to monitor the chemical response to the treatment. Objective clinical parameters of hypertension and tachycardia were followed when present in addition to subjective estimates of acute porphyric symptomatology (abdominal pain, backache, extremity pain and paresthesias, weakness, depression, etc.). 3. At a dosage of approximately 3 mg/kg, diminution of urinary ALA and PBG excretion was achieved in every patients. Hypertension and tachycardia improved in those instances where they were observed in association with the attack. Also, subjective improvements in the clinical status of the patients were observed frequently. 4. Hematin appears to be a promising therapeutic agent for the treatment of acute attack forms of porphyria.     

Ultrafiltration versus intravenous diuretics for patients hospitalized for acute decompensated heart failure.

OBJECTIVES: This study was designed to compare the safety and efficacy of veno-venous ultrafiltration and standard intravenous diuretic therapy for hypervolemic heart failure (HF) patients. BACKGROUND: Early ultrafiltration may be an alternative to intravenous diuretics in patients with decompensated HF and volume overload. METHODS: Patients hospitalized for HF with > or =2 signs of hypervolemia were randomized to ultrafiltration or intravenous diuretics. Primary end points were weight loss and dyspnea assessment at 48 h after randomization. Secondary end points included net fluid loss at 48 h, functional capacity, HF rehospitalizations, and unscheduled visits in 90 days. Safety end points included changes in renal function, electrolytes, and blood pressure. RESULTS: Two hundred patients (63 +/- 15 years, 69% men, 71% ejection fraction < or =40%) were randomized to ultrafiltration or intravenous diuretics. At 48 h, weight (5.0 +/- 3.1 kg vs. 3.1 +/- 3.5 kg; p = 0.001) and net fluid loss (4.6 vs. 3.3 l; p = 0.001) were greater in the ultrafiltration group. Dyspnea scores were similar. At 90 days, the ultrafiltration group had fewer patients rehospitalized for HF (16 of 89 [18%] vs. 28 of 87 [32%]; p = 0.037), HF rehospitalizations (0.22 +/- 0.54 vs. 0.46 +/- 0.76; p = 0.022), rehospitalization days (1.4 +/- 4.2 vs. 3.8 +/- 8.5; p = 0.022) per patient, and unscheduled visits (14 of 65 [21%] vs. 29 of 66 [44%]; p = 0.009). No serum creatinine differences occurred between groups. Nine deaths occurred in the ultrafiltration group and 11 in the diuretics group. CONCLUSIONS: In decompensated HF, ultrafiltration safely produces greater weight and fluid loss than intravenous diuretics, reduces 90-day resource utilization for HF, and is an effective alternative therapy. (The UNLOAD trial; http://clinicaltrials.gov/ct/show/NCT00124137?order=1; NCT00124137).     

Severe hypophosphataemia induced by glucose-insulin-potassium therapy. A case report and proposal for altered protocol

A case is described where severe hypophosphataemia was induced by a widely used protocol for glucose-insulin-potassium (GIK) infusion. Hypophosphataemia was found to be a universal sequel to the use of this infusion. A new regimen for administering this agent was designed, and shown to lack the potentially serious side effect of phosphate depletion.