Target Blood Pressure and Combination Therapy: Focus on Angiotensin Receptor Blockers Combination with Either Calcium Channel Blockers or Beta Blockers.

BACKGROUND: The target blood pressure has changed many times in the guidelines in past years. However, there is always a question; is it good to lower blood pressure below 120/80 or not? Control of blood pressure in hypertension is very important in reducing hypertension-modified organ damage. So, the guidelines recommend combining more than one antihypertensive drug to reach the target blood pressure goal. RESULTS: Combination therapy is recommended by guidelines to reach the blood pressure goal. The guidelines recommend many combinations, such as the combination of angiotensin receptor blockers with either calcium channel blockers (CCB) or beta-blocker (BB). Angiotensin receptor blocker (ARB) combination with CCB has gained superiority over other antihypertension drug combinations because it reduces blood pressure and decreases the incidence of CV events and organ damage. BB combinations are recommended by guidelines in patients with ischemic events but not all hypertensive patients. Unfortunately, the new generation BB, for example, nebivolol, has a vasodilator effect, making it new hope for BB. CONCLUSION: Combination therapy is a must in treating the hypertensive patient. The new generation BBs may change the recommendations of guidelines because they have an effect that is similar to CCBs.

Role of Sedation and Analgesia during Noninvasive Ventilation: Systematic Review of Recent Evidence and Recommendations.

Aim: This systematic review aimed to investigate the drugs used and their potential effect on noninvasive ventilation (NIV). Background: NIV is used increasingly in acute respiratory failure (ARF). Sedation and analgesia are potentially beneficial in NIV, but they can have a deleterious impact. Proper guidelines to specifically address this issue and the recommendations for or against it are scarce in the literature. In the most recent guidelines published in 2017 by the European Respiratory Society/American Thoracic Society (ERS/ATS) relating to NIV use in patients having ARF, the well-defined recommendation on the selective use of sedation and analgesia is missing. Nevertheless, some national guidelines suggested using sedation for agitation. Methods: Electronic databases (PubMed/Medline, Google Scholar, and Cochrane library) from January 1999 to December 2019 were searched systematically for research articles related to sedation and analgosedation in NIV. A brief review of the existing literature related to sedation and analgesia was also done. Review results: Sixteen articles (five randomized trials) were analyzed. Other trials, guidelines, and reviews published over the last two decades were also discussed. The present review analysis suggests dexmedetomidine as the emerging sedative agent of choice based on the most recent trials because of better efficacy with an improved and predictable cardiorespiratory profile. Conclusion: Current evidence suggests that sedation has a potentially beneficial role in patients at risk of NIV failure due to interface intolerance, anxiety, and pain. However, more randomized controlled trials are needed to comment on this issue and formulate strong evidence-based recommendations. How to cite this article: Karim HMR, Sarc I, Calandra C, Spadaro S, Mina B, Ciobanu LD, et al. Role of Sedation and Analgesia during Noninvasive Ventilation: Systematic Review of Recent Evidence and Recommendations. Indian J Crit Care Med 2022;26(8):938-948.

A meta-analysis showing the effect of surgical site wound infections and associated risk factors in neonatal surgeries.

A meta-analysis was performed to assess the effect of surgical site wound infections and risk factors in neonates undergoing surgery. A systematic literature search up to January 2022 incorporated 17 trials involving 645 neonates who underwent surgery at the beginning of the trial; 198 of them had surgical site wound infections, and 447 were control for neonates. The statistical tools like the dichotomous or continuous method used within a random or fixed-influence model to establish the odds ratio (OR) and mean difference (MD) with 95% confidence intervals (CIs) to evaluate the risk factors and influence of surgical site wound infections in neonates undergoing surgery. Surgical site wound infections had significantly higher mortality with OR value 2.03 at 95% CI 1.40-2.95 with P-value <0.001, the longer length of hospital stay (MD, 31.88; 95% CI, 18.17-45.59, P < 0.001), and lower birthweight of neonates (MD, -0.30; 95% CI, -0.53 to -0.07, P = 0.01) compared with neonates with no surgical site wound infections undergoing surgery. However, no remarkable change was observed with surgical site wound infections in the gestational age at birth of neonates (MD, -0.70; 95% CI, -1.46 to 0.05, P = 0.07), and the preoperative antibiotic prophylaxis (OR, 1.28; 95% CI, 0.57-2.87, P = 0.55) compared with no surgical site wound infections for neonates undergoing surgery. Surgical site wound infections had significantly higher mortality, a longer length of hospital stay, and lower birthweight of neonates. However, they had no statistically significant difference in the gestational age at birth of neonates and the preoperative antibiotic prophylaxis compared with no surgical site wound infections for neonates undergoing surgery. Furthermore, evidence is needed to confirm the outcomes.

Conscious sedation compared to general anesthesia for intracranial mechanical thrombectomy: A meta-analysis.

INTRODUCTION: Endovascular therapy is the standard of care for severe acute ischemic stroke caused by large-vessel occlusion in the anterior circulation, but there is a debate on the optimal anesthetic approach during this therapy. Meta-analyses of observational studies suggest that general anesthesia increases disability and death compared with conscious sedation However, their results are conflicting. This meta-analysis study was performed to assess the relationship between the effects of general anesthesia compared to conscious sedation during endovascular therapy for acute ischemic stroke. METHODS: Through a systematic literature search up to August 2020, 18 studies included 4,802 subjects at baseline with endovascular therapy for acute ischemic stroke and reported a total of 1,711 subjects using general anesthesia and 1,961 subjects using conscious sedation were found. They recorded relationships between the effects of general anesthesia compared to conscious sedation during endovascular therapy for acute ischemic stroke. Odds ratio (OR) or Mean differences (MD) with 95% confidence intervals (CIs) were calculated between the effect of general anesthesia compared to conscious sedation during endovascular therapy for acute ischemic stroke using the dichotomous or contentious methods with a random or fixed-effect model. RESULTS: No significant difference were found between general anesthesia and conscious sedation during the endovascular therapy for acute ischemic stroke in functional independence at 90 days (OR, 0.78; 95% CI, 0.44-1.40, p = 40); successful recanalization at 24 hr (OR, 1.23; 95% CI, 0.62-2.41, p = 55); mortality at 90 days (OR, 1.36; 95% CI, 0.83-2.24, p = .22); interventional complication (OR, 1.24; 95% CI, 0.76-2.02, p = .40); symptomatic intracranial hemorrhage (OR, 0.64; 95% CI, 0.41-0.99, p = .05); aspiration pneumonia (OR, 0.96; 95% CI, 0.58-1.58, p = .87); and National Institute of Health Stroke Scale score after 24 hr (MD, 0.38; 95% CI, -1.15-1.91, p = .62); with relative relationship favoring general anesthesia only in decreasing the symptomatic intracranial hemorrhage. CONCLUSIONS: General anesthesia has no independent relationship compared to conscious sedation during the endovascular therapy for acute ischemic stroke with a relative relationship favoring general anesthesia only in decreasing the symptomatic intracranial hemorrhage. This relationship encouraged us to recommend either anesthetic strategy during the endovascular therapy for acute ischemic stroke with no possible fear of higher complication.

Ginseng Consumption Possible Effect on Liver Cancer: A Meta-Analysis.

INTRODUCTION: Ginseng is associated to the reduction of the risk of liver-cancer and some time is used as adjuvant therapy to treat liver-cancer, but its outcome remains uncertain. Hence, the present study aimed to determine the association between Ginseng consumption and liver-cancer. METHODS: By a systematic-literature search up to Decamber-2019, 9-studies included 13,766 subjects, 9235 Ginseng consumer. Odds ratio (OR) with 95% confidence intervals (CIs) was determined comparing Ginseng consumption and liver-cancer relationship using the dichotomous method with a fixed-effect or random-effect models. RESULTS: Subjects consuming Ginseng had a significantly lower risk of developing liver-cancer than those not consuming Ginseng (OR, 0.46; 95% CI, 0.40-0.52, p < 0.001). Also, there was a significant relationship between Ginseng consumption as adjuvant-therapy and disease control rate (OR, 4.47; 95% CI, 2.41-8.28, p < 0.001), Karnofsky Performance Scale (OR, 4.31; 95% CI, 1.80-10.36, p = 0.001), response to chemotherapy rate (OR, 1.79; 95% CI, 1.05-3.02, p = 0.03) and decline of leukocyte count (OR, 0.17; 95% CI, 0.07-0.42, p < 0.001). However, there was no significant effect, but relatively favoring Ginseng consumption, between Ginseng consumption as adjuvant-therapy and one year survival rate (OR, 1.48; 95% CI, 0.78-2.81, p = 0.23), two year survival rate (OR, 1.69; 95% CI, 0.87-3.25, p = 0.12) gastrointestinal dysfunction (OR, 0.55; 95% CI, 0.17-1.79, p = 0.32), and the hepatic dysfunction (OR, 1.15; 95% CI, 0.59-2.22, p = 0.68). CONCLUSIONS: Ginseng may have an independent relationship with reducing liver-cancer incidence when administrated to healthy subjects as a supplement and with reducing cancer-chemotherapy related outcomes risk when administrated with chemotherapy as adjuvant therapy.

Impact of Advanced Patient Counseling Using a Training Device and Smartphone Application on Asthma Control.

BACKGROUND: Pressurized metered-dose inhalers (pMDIs) are among the most commonly used aerosol delivery devices. Poor lung deposition from a pMDI is often a result of incorrect inhalation technique. The aim of this study was to compare the impact of combining a newly released training device with a smartphone application (advanced counseling) in asthma control to the impact of traditional verbal training. METHODS: A total of 371 subjects with asthma were divided into 2 groups: advanced counseling (n = 187) and verbal counseling (n = 184). Both groups had 3 visits, each meeting being a month apart. At each visit, lung function (ie, FEV1, ratio of FEV1 to forced vital capacity [FEV1/FVC], and peak expiratory flow) were measured, an asthma control test was given, and subjects were trained in the correct inhalation technique. Inhalation flow through the pMDI was also recorded at each visit because the correct pMDI technique requires an inspiratory flow of < 60 L/min. RESULTS: In the advanced counseling group, lung function significantly improved after both the first and the second visit (P < .001), whereas in the verbal group, lung function improved significantly only after the second visit (P < .001). Although the inspiratory flow through the pMDI improved significantly in both groups, it was closest to the target range in the advanced counseling group. In addition, more subjects in the advanced counseling group had monthly increases of ≥ 3 points in their asthma control test scores compared to the verbal counseling group. CONCLUSIONS: The use of a training device with a smartphone application in conjunction with traditional verbal counseling in pMDI technique resulted in significant improvements in asthma control compared to traditional verbal counseling in pMDI technique alone.

Evaluation of Disposable and Traditional Accessory Devices for Use With a Pressurized Metered-Dose Inhaler.

BACKGROUND: The use of accessory devices with pressurized metered-dose inhalers (pMDIs) enhances aerosol delivery and helps overcome any lack of patient coordination when using the pMDI. The use of accessory devices could be influenced by the efficacy, availability, and cost of these devices. The aim of this study was to compare drug delivery with the pMDI alone and with non-antistatic and antistatic accessory devices. METHODS: The total emitted dose and aerodynamic characterization of salbutamol particles were measured for the pMDI alone and for the pMDI combined with 4 different accessory devices: a homemade spacer, the Dolphin spacer, the DispozABLE paper spacer, and the AeroChamber Plus valved holding chamber. Aerodynamic characterization was analyzed with an Andersen cascade impactor at an inhalation flow of 28.3 L/min, and drug deposition was measured with high-performance liquid chromatography. RESULTS: The mean ± SD total emitted dose from the pMDI alone, 155.2 ± 20.5 µg, was the greatest of all modalities, and the difference was significant (P < .001). The homemade and Dolphin spacers had the highest mean ± SD deposited amounts of salbutamol remaining on their walls (ie, 124.1 ± 11.1 µg and 131.5 ± 11.8 µg, respectively). The mean ± SD total emitted doses with the AeroChamber Plus valved holding chamber (61.9 ± 8.9 µg) and the DispozABLE paper spacer (76.4 ± 8.6 µg) were significantly higher than the emitted doses with the other devices. The mean ± SD fine-particle doses emitted with the AeroChamber plus valved holding chamber (51.4 ± 4.7 µg) and the DispozABLE paper spacer (39.7 ± 5.6 µg) were significantly higher than those with the other devices. The AeroChamber Plus valved holding chamber had the lowest mass median aerodynamic diameter (MMAD) values, but there were no statistically significant differences in MMAD between any of the combinations of pMDI and accessory device. CONCLUSIONS: The valved holding chamber and the paper spacer had better aerodynamic characteristics than the other devices tested. We consider the antistatic devices to be the optimum devices for aerosol delivery due to their high efficacy compared to non-antistatic devices.

Effect of Oxygen Flow on Aerosol Delivery From a Nebulizer With a Holding Chamber.

BACKGROUND: A new holding chamber was designed to be used with a vibrating mesh nebulizer to increase the total inhalable dose for patients. It facilitates intermittent and continuous nebulization as well as the optional supply of supplemental oxygen via a T-piece with a mouthpiece adapter. This study aimed to evaluate the effect of oxygen introduction in the new holding chamber on aerosol delivery using a vibrating mesh nebulizer. METHODS: The study was divided into 2 parts. First, the total inhalable dose of 1 mL of a respirable solution (nominal dose of 5,000 µg-salbutamol) was determined using a breathing simulator set to provide a tidal volume of 500 mL, a breathing frequency of 15 breaths/min, and an inspiratory:expiratory ratio of 1:1 for adults as a quiet-breathing pattern. Three experimental nebulizer setups were used: a vibrating mesh nebulizer with the holding chamber and oxygen set at 6 L/min, a vibrating mesh nebulizer with the holding chamber and no oxygen, and a vibrating mesh nebulizer with the T-piece. Aerodynamic particle size characterizations were determined using cooled Andersen cascade impaction at an inhalation flow of 15 L/min. Second, we performed an in vivo study involving 12 healthy non-smoking subjects (6 female) who were > 18 y old with an average FEV1 > 90% of predicted. Using normal tidal breathing, subjects inhaled 1 mL of nebulized salbutamol (5,000 µg) through the vibrating mesh nebulizer with the holding chamber with and without oxygen and through the vibrating mesh nebulizer with a T-piece. To analyze salbutamol content, urine samples were obtained 30 min after dosing as an index of lung deposition, and their urine was cumulatively collected for 24 h as an index of systemic absorption. RESULTS: The holding chamber significantly increased the total inhalable dose or amount of salbutamol excreted in the first 30 min, as well as the amount of salbutamol excreted over a 24-h period compared to the dose received with the vibrating mesh nebulizer with a T-piece (P = .005, P = .034, and P = .02, respectively), and relatively decreased the mass median aerodynamic diameter, although the difference was not significant. However, when oxygen was introduced in the holding chamber, the total inhalable dose, or amount of salbutamol excreted in the first 30 min, significantly decreased compared to use without oxygen (P = .003, P = .03 respectively). No significant difference was found between the vibrating mesh nebulizer with the holding chamber with oxygen and the vibrating mesh nebulizer with a T-piece. CONCLUSIONS: The vibrating mesh nebulizer with a holding chamber and without oxygen resulted in much better aerosol delivery compared to vibrating mesh nebulizer with a holding chamber and with oxygen delivery and to the vibrating mesh nebulizer with a T-piece. The use of oxygen with the holding chamber significantly decreased aerosol delivery and its benefit, and recommended flow should be reevaluated.

Aerosol Delivery Through an Adult High-Flow Nasal Cannula Circuit Using Low-Flow Oxygen.

BACKGROUND: There has been a growing trend toward delivering aerosolized medications using high-flow nasal cannula (HFNC). In some cases, patients who do not require high-flow oxygen to maintain adequate oxygenation may benefit from aerosol delivery while receiving low-flow oxygen via HFNC. The objective of this study was to quantify and compare the relative pulmonary and systemic delivery of salbutamol, with 2 different nebulizers, in patients with COPD receiving low-flow oxygen therapy through an HFNC. METHODS: Subjects were randomized to receive study doses of 5 mg salbutamol nebulized by either a jet nebulizer or a vibrating mesh nebulizer with a T-piece or spacer on days 1, 3, and 5 of admission. Subjects using the large spacer also received 2 puffs (100 µg each) of salbutamol via a pressurized metered-dose-inhaler prior to the nebulizer dose. Urinary salbutamol excretion 30 min post-inhalation and pooled samples of urinary salbutamol excretion up to 24 h post-inhalation were measured. On day 2, ex vivo studies were performed with salbutamol collected on filters placed between the HFNC and nebulizer, with drug eluted from filters and analyzed to determine inhaled dose. RESULTS: Twelve subjects (6 females), age 51.3 ± 11.2 y, were included. The vibrating mesh nebulizer demonstrated higher urinary salbutamol excretion at 30 min and 24 h post-inhalation compared to a jet nebulizer (P = .001 and P = .02, respectively). No significant difference was found between the T-piece and large-spacer configurations, even though the spacer provided a significantly larger emitted aerosol dose at the opening of the HFNC (P = .002). CONCLUSIONS: Aerosolized medication could be efficiently combined with low-flow oxygen, via HFNC, in COPD subjects without the need to interrupt the gas supply. The vibrating mesh nebulizer delivered larger doses to subjects compared to the jet nebulizer. However, there was no benefit of using the large spacer with HFNC in low-flow delivery, because the small inner diameter of the HFNC does not allow larger aerosol droplet sizes (preserved by the spacer) to reach the subject.

Performance of Large Spacer Versus Nebulizer T-Piece in Single-Limb Noninvasive Ventilation.

BACKGROUND: Predosing patients with COPD with salbutamol by using a pressurized metered-dose-inhaler (pMDI) as a bronchodilator was hypothesized to improve the distribution of the subsequent nebulized dose. This study determined the effect of a pMDI preliminary bronchodilator dose on the aerosol delivered by a mesh nebulizer during single-limb noninvasive ventilation. METHODS: Twelve subjects with COPD who received noninvasive ventilation were enrolled in a randomized, open-label, urinary pharmacokinetic study. A bi-level ventilator with a dry single-limb circuit and the fixed expiratory port was set in the spontaneous mode, with initial inspiratory and expiratory pressures of 20 and 5 cm H2O respectively, a 1:3 inspiratory-expiratory ratio, and 15 breaths/min. Salbutamol was administered via a mesh nebulizer with a large spacer or T-piece placed between the fixed-orifice expiratory valve and the oronasal mask. In vivo dosing methods were randomized for days 1, 3, and 5 of the study. On each day, a 1-mL respirable solution that contained 5,000 µg salbutamol was nebulized by using a mesh nebulizer with 3 setting: (1) T-piece, (2) large spacer, and (3) large spacer plus pMDI. Only with the large spacer plus pMDI setting, 2 pMDI doses, which contained 100 µg salbutamol each, were actuated before nebulization. Urine samples were collected at 0.5 h (as an index of pulmonary bioavailability) and pooled up to 24 h after dosing (as an index of systemic absorption). On day 2, ex vivo studies were performed for the 3 setting with salbutamol collected onto filters placed before the mask. The drug was eluted from the filters and analyzed to determine the inhaled dose. RESULTS: A large spacer plus pMDI showed a trend to deliver a higher fraction (percentage of nominal dose) of both ex vivo filters and 0.5-h urinary salbutamol. The 0.5-h urinary salbutamol excreted with a large spacer plus pMDI (1.99%) was larger than with the T-piece (1.73%) and large spacer (1.78%). This trend did not extend to the 24-h levels, in which bioavailability with the large spacer plus pMDI (49.9%) was lower than with the T-piece (52.8%) and with the large spacer (54.3%). However, no differences were significant. CONCLUSIONS: The T-piece and large spacer were equally efficient for salbutamol delivery from the mesh nebulizer in patients with COPD and on single-limb noninvasive ventilation. Adding a preliminary bronchodilator dose by pMDI prenebulization showed a trend toward greater pulmonary bioavailability of nebulized salbutamol and may be worth considering to maximize delivery of salbutamol to patients who are severely ill.

Effects of Fill Volume and Humidification on Aerosol Delivery During Single-Limb Noninvasive Ventilation.

BACKGROUND: The aim of this work was to determine the effect of fill volume and humidification change on aerosol delivery during single-limb noninvasive ventilation (NIV). METHODS: Four groups were recruited, each consisting of 12 subjects (6 females) with COPD receiving NIV. Groups 1 and 3 received inhaled salbutamol with a vibrating mesh nebulizer, and Groups 2 and 4 received inhaled salbutamol with a jet nebulizer. The in vivo study was carried out on days 1 and 3. In groups 1 and 2, 2 fill-volumes were delivered to each subject; 1 mL 5,000 µg/mL salbutamol respirable solution used as it is or diluted to a total of 2 mL using normal saline. In groups 3 and 4, 1 mL 5,000 µg/mL salbutamol respirable solution diluted to 2 mL total volume using normal saline was delivered to each subject with and without humidification. Unchanged salbutamol in urine at 30 min (USAL0.5) and in pooled urine at 24 h (USAL24) was determined. On day 2, the ex vivo study was carried out on subjects using the same experimental setting with a filter placed proximal to their face mask for collection of total inhaled dose of salbutamol (aerosol emitted). RESULTS: The vibrating mesh nebulizer delivered higher USAL0.5, USAL24, and aerosol emitted compared to the jet nebulizer at all fill volumes and humidification conditions (P < .001). Increasing fill volume from 1 mL to 2 mL resulted in a significant increase in USAL0.5, USAL24, and aerosol emitted from the jet nebulizer (P < .05) with an insignificant effect on the vibrating mesh nebulizer. A 2-mL fill volume with the jet nebulizer delivered USAL24 and aerosol emitted comparable to those of 1 mL with the vibrating mesh nebulizer with significantly longer nebulization times (P < .001). Humidification had an insignificant effect on aerosol delivery. CONCLUSIONS: Increasing the fill volume of a jet nebulizer is essential to increase the amount of inhaled medication reaching a subject. In contrast, there is no need to increase fill volumes when using a vibrating mesh nebulizer. There is no need to switch off the humidifier while delivering aerosol through a single-limb NIV circuit.

Effect of a Nebulizer Holding Chamber on Aerosol Delivery.

BACKGROUND: A new holding chamber was designed to be used with the Aerogen Solo nebulizer to increase the aerosol emitted that reach the patient. The aim of this study was to evaluate the efficacy of this holding chamber with the nebulizer and determine its usability with other nebulizers. METHODS: The study was divided into 2 parts. In the first part, aerosol emitted of 1 mL respirable solution (nominal dose of 5000 µg salbutamol), delivered by using the mesh nebulizer, Pro nebulizer, and jet nebulizer, connected to a T-piece or a holding chamber, was determined by using a breathing simulator set to provide a tidal volume of 500 mL, frequency of 15 breaths/min, and the inspiratory-expiratory ratio of 1:1 for adults as the quiet breathing pattern. Aerodynamic particle size characterizations were determined by using a cooled cascade impactor at an inhalation flow of 15 L/min. In the second part of the study, 12 healthy nonsmoking subjects (6 females) >18 y, with an FEV1 > 90% were enrolled. Inhaled aerosol of 1 mL respirable solution (5,000 µg salbutamol) was delivered through the mesh nebulizer-holding chamber and an mesh nebulizer-T-piece using normal tidal breathing. The subjects provided urine samples 30 min after dosing and cumulatively collected their urine for 24 h. The samples were analyzed for salbutamol content. RESULTS: The holding chamber significantly increased aerosol emitted by the 3 nebulizers compared with the T-piece (P < .01) and relatively decreased the mass median aerodynamic diameter but with no significant difference. The mesh nebulizer-holding chamber resulted in significantly higher aerosol emitted compared with any other delivery method tested (P < .01). The mesh nebulizer-holding chamber resulted in higher urine samples 30 min after dosing (as an index of lung deposition) and cumulatively collected urine for 24 h (as an index of systemic absorption) compared with the nebulizer-T-piece (P < .05). CONCLUSIONS: The use of the holding chamber with a jet nebulizer, Pro nebulizer, and the Solo nebulizer significantly increased the aerosol delivery. The Solo nebulizer-holding chamber had the highest aerosol emitted compared with all nebulizer-adapter combinations and higher urine samples 30 min after dosing and cumulatively collected urine for 24 h compared with the nebulizer-T-piece.