Tolerability of a single IV administration of a methylene blue challenge in patients with bipolar disorder: preliminary data from a pharmaco-MRI study

AimsTo summarise the tolerability profile following an infusion of methylene blue (MB), including subjective effects on mood and energy levels and haemodynamic changes, in patients with Bipolar Affective Disorder (BPAD).BackgroundBPAD is associated with mitochondrial dysfunction and impaired cellular energy production. MB is proposed to enhance mitochondria function via rerouting electrons and intracellular reduction of oxidative stress, and is therefore a candidate compound for use as a probe to reveal alterations in brain oxygen metabolism in vivo in patients with BPAD. Although there are reports of MB used as treatment for BPAD, the tolerability and subjective effects of a single IV dose in this population has not yet been defined.MethodUsing a single-blind, randomised, within-subject design, 7 patients with BPAD on stable pharmacological treatment and 6 healthy controls (HCs) received an infusion of 0.5mg/kg MB and a placebo glucose solution one week apart. Visual Analogue Scales (VAS) assessing ‘Mood’ and ‘Energy’ levels were completed by 11 participants, and blood pressure (BP), heart rate (HR) and any subsequent side effects were recorded before and after infusions.ResultA significant, albeit very small, effect of MB on ‘Mood’ levels relative to placebo was demonstrated, independent of groups (change relative to baseline: 5.5% ± 11 increase (placebo) vs -1.6 % ± 9.5 reduction (MB); p = 0.027). Although there was no effect of MB on energy levels in either group, there appeared to be a trend for a general group difference in ‘Energy’ levels across all trials, with lower ratings in BPAD patients (p = 0.058).There was a trend for significantly lower post-infusion HR relative to pre-infusion (-6.4 ± 8.8 bpm, p = 0.07. Diastolic BP was higher (3.0 ± 7.8mmHg, p = 0.039). These effects were independent of groups and drug. The most common side effect with MB was mild/moderate pain at infusion site (n = 10/13), resolving within median 32.5 minutes (IQR 6-102), and discoloured urine in 7/13 subjects lasting median 44.5 hours (IQR 36-59). No difference in frequency of side effects reported between groups.ConclusionAlthough limited by small sample size, this tolerability analysis demonstrates a acceptable profile of effects of MB on subjective ratings and blood pressure, in both BPAD and HCs. Common side effects of discoloured urine and pain at infusion site are in line with previous reports in the literature. We observed a small effect of MB on mood ratings which could be related to the discomfort experienced during infusion.

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Somatic Comorbidities and Cardiovascular Safety in Ketamine Use for Treatment-Resistant Depression

Medicina ◽

10.3390/medicina57030274 ◽

2021 ◽

Vol 57 (3) ◽

pp. 274

Author(s):

Joanna Szarmach ◽

Wiesław Jerzy Cubała ◽

Adam Włodarczyk ◽

Maria Gałuszko-Węgielnik

Keyword(s):

Diabetes Mellitus ◽

Blood Pressure ◽

Heart Rate ◽

Small Sample ◽

Tolerability Profile ◽

Acute Administration ◽

Treatment Resistant Depression ◽

Treatment Resistant ◽

Somatic Comorbidities ◽

Resistant Depression

Background and Objectives: There is evidence for ketamine efficacy in treatment-resistant depression (TRD). Several safety and tolerability concerns arise that some psychotropic agents may provide blood pressure or/and heart rate alterations. The aim of this study is to review blood pressure measurements in course of the treatment with ketamine on treatment refractory inpatients with somatic comorbidities in the course of MDD and BP. Materials and Methods: The study population of 49 patients comprised MDD and BP subjects treated with ketamine registered in the naturalistic observational protocol of treatment-resistant mood disorders (NCT04226963). Results: The conducted analysis showed that among people suffering from hypertension there is a higher increase in systolic blood pressure (RR) after infusion 2 (p = 0.004) than among people who do not suffer from hypertension. Patients with hypertension have a higher increase in diastolic RR compared to those not suffering from hypertension (p = 0,038). Among the subjects with diabetes mellitus, significant differences occurred for infusions 2 (p = 0.020), 7 (p = 0.020), and 8 (p = 0.035) for heart rate (HR), compared to subjects without diabetes mellitus. A higher increase in diastolic RR was noted in the group of subjects suffering from diabetes mellitus (p = 0.010) compared to those who did not. In the hyperlipidemic patients studied, a significantly greater decrease in HR after infusion 5 (p = 0.031) and systolic RR after infusion 4 (p = 0.036) was noted compared to nonpatients. People after a stroke had significantly higher increases in diastolic RR after infusions 4 (p = 0.021) and 6 (p = 0.001) than those who did not have a stroke. Patients suffering from epilepsy had a significantly greater decrease in systolic RR after the 8th infusion (p = 0.017) compared to those without epilepsy. Limitations: The study may be underpowered due to the small sample size. The observations apply to inhomogeneous TRD population in a single-site with no blinding and are limited to the acute administration. Conclusions: This study supports evidence for good safety and tolerability profile for short-term IV ketamine use in TRD treatment. However, risk mitigation measures are to be considered in patients with metabolic and cardiovascular comorbidities.

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Methylene blue versus vasopressin analog for refractory septic shock in the preterm neonate: A randomized controlled trial

Journal of Neonatal-Perinatal Medicine ◽

10.3233/npm-210824 ◽

2021 ◽

pp. 1-9

Author(s):

R. Ismail ◽

H. Awad ◽

R. Allam ◽

O. Youssef ◽

M. Ibrahim ◽

...

Keyword(s):

Blood Pressure ◽

Septic Shock ◽

Methylene Blue ◽

Randomized Controlled Trial ◽

Side Effects ◽

Preterm Neonate ◽

Controlled Trial ◽

Randomized Controlled ◽

Arterial Blood ◽

Refractory Septic Shock

BACKGROUND: Refractory septic shock in neonates is still associated with high mortality, necessitating an alternative therapy, despite all currently available treatments. This study aims to assess the vasopressor effect of methylene blue (MB) in comparison to terlipressin (TP) as adjuvant therapy for refractory septic shock in the preterm neonate. METHODS: A double-blinded randomized controlled trial was conducted in the Neonatal Intensive Care Units at Ain Shams University, Egypt. Thirty preterm neonates with refractory septic shock were randomized to receive either MB or TP as an adjuvant to conventional therapy. Both MB and TP were administered as an intravenous loading dose followed by continuous intravenous infusion. The hemodynamic variables, functional echocardiographic variables, and oxidant stress marker were assessed over a 24 h period together with the side effects of MB. RESULTS: MB causes significant improvement in mean arterial blood pressure with a significant decrease of the norepinephrine requirements (1.15±0.21μm/kg/min at baseline vs. 0.55±0.15μm/kg/min at 24 h). MB infusion causes an increase of the pulmonary pressure (44.73±8.53 mmHg at baseline vs. 47.27±7.91 mmHg after 24 h) without affecting the cardiac output. Serum malonaldehyde decreased from 5.45±1.30 nmol/mL at baseline to 4.40±0.90 nmol/mL at 24 h in the MB group. CONCLUSION: Administration of MB to preterm infants with refractory septic shock showed rapid increases in systemic vascular resistance and arterial blood pressure with minimal side effects.

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Baroreflex activation therapy for resistant hypertension: results from mid-term prospective ambulatory blood pressure registry

European Heart Journal ◽

10.1093/ehjci/ehaa946.2784 ◽

2020 ◽

Vol 41 (Supplement_2) ◽

Author(s):

M Sindt ◽

T Madej ◽

S Grimm ◽

M Knaut

Keyword(s):

Blood Pressure ◽

Side Effects ◽

Pressure Drop ◽

Arterial Hypertension ◽

Antihypertensive Drugs ◽

Drug Resistant ◽

Baroreflex Activation Therapy ◽

Activation Therapy ◽

Resistant Arterial Hypertension

Abstract Objectives First generation baroreflex activation therapy (BAT) devices showed clinical efficacy in patients with drug-resistant arterial hypertension (AHT), but the safety profile was insufficient. Data regarding efficacy of second-generation devices were generated mostly from office blood pressure (BP) measurements or short-term 24-hour ambulatory blood pressure measurements (ABPM). We present a mid-term prospective registry to evaluate the efficacy and safety of recent BAT devices. Purpose The purpose of our study was to find a method that helps patients with drug-resistant arterial hypertension to control their blood pressure. Further we sought to reduce the overall amount of antihypertensive drugs to lessen side effects, as well as the effects of polypharmacy. Methods All patients receiving Barostim neo between November 2013 and June 2019 for resistant AHT were prospectively included into this observational study. ABPM was performed at baseline, in 3-month intervals in the first year after BAT implantation and in 6-month intervals afterwards for up to 42 months. Patients were assigned into two groups of responders and non-responders. Non-responders had a mean blood pressure drop (BPD) below 5mmHg. Responders in turn were categorized into 3 sub-groups (low-BPD between 5–9 mmHg, medium-BPD between 10–19 mmHg and high-BPD ≥20 mmHg). The primary efficacy end-points were changes in systolic and diastolic BP and number of antihypertensive medications. The primary safety end point was BAT-related major adverse events (MAE). Results 64 patients (mean age 63 years, 67% males) were included. Only patients who completed a 24-hour ABPM during a follow up were counted in the statistical analysis. We had an overall responder rate of 67.8%. Out of those 15.4% had low-BPD, 38.4% medium-BPD and 46.2% had a high-BPD. Systolic BP decreased over the 3.5-years period from 168±17 mmHg to 149±19 mmHg (n=19, mean change −18.8 mmHg; 95% confidence interval [CI]: −29.32 to −8.36; p<0.0007). Diastolic BP decreased from 97±16 to 85±12 mmHg (n=19, mean change −11.7 mmHg; 95% CI: −19.2 to −4.2; p<0.0021). The mean number of antihypertensive drugs was reduced from 6.9±1.3 to 5.2±1.5 (n=19, mean change −1.7; 95% CI: −0.8 to −0.27; p<0.0009). The time course of primary end-points is shown in Fig.1. Freedom from BAT-related MAE was 93.5%. 4 perioperative complications (1 pocket bleeding, 1 pocket infection, 1 N. hypoglossus palsy, 1 hoarseness) resolved without residual side effects. There were five non BAT related deaths (7,8%) in the follow up period. Conclusion Systolic and diastolic ABP, as well as number and dosage of antihypertensive drugs decreased significantly during 3.5-years follow-up after Barostim neo implantation in 64 consecutive patients (of whom 62 completed at least one follow-up). No MAE associated with BAT were observed after the perioperative period. However, further controlled trials are needed to confirm the long-term efficacy of BAT. Figure 1. Mean blood pressure drop Funding Acknowledgement Type of funding source: None

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Arterial hypertension + past stroke – a case report

Medycyna Faktów ◽

10.24292/01.mf.0321.16 ◽

2021 ◽

Vol 14 (3) ◽

pp. 324-326

Author(s):

Maria Łukasiewicz ◽

Marta Swarowska-Skuza

Keyword(s):

Blood Pressure ◽

Case Report ◽

Chronic Disease ◽

Side Effects ◽

Arterial Hypertension ◽

Antihypertensive Therapy ◽

Systolic Hypertension ◽

The Elderly ◽

Isolated Systolic Hypertension ◽

Special Group

Arterial hypertension, as a very widespread chronic disease, and thus differing in both pathomechanism and course in patients, requires a significant individualization of pharmacotherapy. One such special group is the elderly. Both the low-renin pathomechanism of arterial hypertension and its phenotype (isolated systolic hypertension) imply the choice of a specific pharmacotherapy. Additionally, in this group, side effects should be observed much more vigilantly, while target blood pressure values should be treated more liberally. An example of antihypertensive therapy in a patient belonging to the group described is presented in the following case.

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Abstract W P224: Higher Pre-Hospital Blood Pressure Prolongs Door to Needle Thrombolysis Times

Stroke ◽

10.1161/str.46.suppl_1.wp224 ◽

2015 ◽

Vol 46 (suppl_1) ◽

Author(s):

Digvijaya Navalkele ◽

Chunyan Cai ◽

Mohammad Rahbar ◽

Renganayaki Pandurengan ◽

Tzu-Ching Wu ◽

...

Keyword(s):

Blood Pressure ◽

Ischemic Stroke ◽

Acute Ischemic Stroke ◽

Small Sample Size ◽

Heart Association ◽

Small Sample ◽

Categorical Variables ◽

Continuous Variables ◽

Intravenous Tissue Plasminogen Activator ◽

Number Of Patients

Background: Per American Heart Association guidelines, blood pressure (BP) should be < 185/110 to be eligible for intravenous tissue plasminogen activator (tPA). It is shown that door to needle (DTN) time is prolonged in patients who require anti-hypertensive medications prior to thrombolysis in the emergency department (ED). To our knowledge, no studies have focused on pre-hospital BP and its impact on DTN times. We hypothesize that DTN times are longer for patients with higher pre-hospital BP. Methods: We conducted a retrospective review of acute ischemic stroke patients who presented between 1/2010 and 12/2010 to our ED through Emergency Medical Services (EMS) within 3-hrs of symptom onset. Patients were identified from our registry and categorized into two groups: Pre-hospital BP ≥ 185/110 (Pre-hsp HBP) and < 185/110 (Pre-hsp LBP). BP records were abstracted from EMS sheets. Two groups were compared using two-sample t-test or Wilcoxon rank sum test for continuous variables and Chi-square test or Fisher’s exact test for categorical variables. Results: A total of 107 consecutive patients were identified. Out of these, 75 patients (70%) were treated with tPA. Among the patients who received thrombolysis, 35% had pre-hospital BP ≥ 185/110 (n= 26/75). Greater number of patients required anti-hypertensive medications in ED in high BP group compared to low BP group (Pre-hsp HBP n= 14/26, 54%; Pre-hsp LBP n= 13/49, 27%, p < 0.02). Mean door to needle times were significantly higher in Pre-hsp HBP group. (mean ± SD 87.5± 34.2 Vs. 59.7±18.3, p<0.0001). Analysis of patients only within the Pre-hsp HBP group (n= 26) revealed that DTN times were shorter if patients received pre-hsp BP medications compared to patients in the same group who did not receive pre-hsp BP medication (n= 10 vs 16; mean ± SD 76.5 ± 25.7 Vs. 94.3 ± 37.7, p = 0.20) Conclusion: Higher pre-hospital BP is associated with prolonged DTN times and it stays prolonged if pre-hospital high BP remains untreated. Although the later finding was not statistical significant due to small sample size, pre-hospital blood pressure control could be a potential area for improvement to reduce door to needle times in acute ischemic stroke.

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Methylene blue is not contraindicated to treat hemodynamic instability in pediatric and neonate patient

Current Pediatric Reviews ◽

10.2174/1573396317666210816105812 ◽

2021 ◽

Vol 17 ◽

Author(s):

Walusa A. Gonçalves-Ferri ◽

Agnes A.S. Albuquerque ◽

Patricia Martinez Evora ◽

Paulo R.B. Evora

Keyword(s):

Methylene Blue ◽

Side Effects ◽

Infusion Rate ◽

Case Reports ◽

Hemodynamic Instability ◽

Exclusion Criteria ◽

Old Patients ◽

Randomized Clinical Study ◽

Dose Infusion ◽

Administration Timing

: The present review was carried out to describe publications on the use of methylene blue (MB) in pediatrics and neonatology, discussing dose, infusion rate, action characteristics and possible benefits for a pediatric patient group. The research was performed on the data sources PubMed, BioMed Central, and Embase (updated on Aug 31, 2020) by two independent investigators. The selected articles included human studies that evaluated MB use in pediatric or neonatal patients with vasoplegia due to any cause, regardless of the applied methodology. The MB use and 0 to18-years-old patients with vasodilatory shock were the adopted criteria. Exclusion criteria were the use of MB in patients without vasoplegia and patients ≥ 18-years-old. The primary endpoint was the increase in mean arterial pressure (MAP). Side effects and dose were also evaluated. Eleven studies were found of which 10 were case reports and 1 was a randomized clinical study. Only two of these studies were with neonatal patients (less than 28 days-old), reporting a small number of cases (1 and 6). All studies described positive action of MB on MAP, allowing the decrease of vasoactive amines in several of them. No severe side effects or death related to the use of the medication was reported. The maximum dose used was 2 mg/kg, but there was no consensus on the infusion rate and drug administration timing. Finally, no theoretical or experimental basis sustains the decision to avoid MB in children claiming it can cause pulmonary hypertension. The same goes for the concern of a possible deleterious effect on inflammatory distress syndrome.

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F85. Reported Side-Effects, Weight and Blood Pressure After Repeated Sessions of Transcranial Photobiomodulation

Biological Psychiatry ◽

10.1016/j.biopsych.2019.03.622 ◽

2019 ◽

Vol 85 (10) ◽

pp. S245

Author(s):

Richard Norton ◽

Marco Caldieraro ◽

David Mischoulon ◽

Nhi-Ha Trinh ◽

Maren Nyer ◽

...

Keyword(s):

Blood Pressure ◽

Side Effects

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Acute Pharmacological Effects and Oral Fluid Concentrations of the Synthetic Cannabinoids JWH-122 and JWH-210 in Humans After Self-Administration: An Observational Study

Frontiers in Pharmacology ◽

10.3389/fphar.2021.705643 ◽

2021 ◽

Vol 12 ◽

Author(s):

Lucia Martínez ◽

Nunzia La Maida ◽

Esther Papaseit ◽

Clara Pérez-Mañá ◽

Lourdes Poyatos ◽

...

Keyword(s):

Blood Pressure ◽

Observational Study ◽

Oral Fluid ◽

Short Form ◽

Subjective Effects ◽

Synthetic Cannabinoids ◽

Drug Effects ◽

Pharmacological Effects ◽

Self Administration ◽

Potential Health

Synthetic cannabinoids (SCs) are a group of new psychoactive drugs used recreationally with potential health risks. They are monitored by the EU Early Warning System since 2010 due to severe adverse effects on consumers. JWH-122 and JWH-210 are naphthoylindole SCs and potent cannabinoid receptor CB1 and CB2 agonists. Information about the effects of SCs usually is available from intoxication cases and surveys, and few studies on humans after controlled administration or observational/naturalistic studies using standardized measures of cardiovascular and subjective effects are available. The aim of this study was to evaluate the acute pharmacological effects of JWH-122 and JWH-210 recreational consumption in a 4 h observational study and assess their disposition in oral fluid (OF). Sixteen volunteers self-administered 1 mg dose of JWH-122 (n = 8) or 2.25 mg mean dose of JWH-210 (range 2–3 mg, n = 8) by inhalation (smoking). Physiological parameters including blood pressure (systolic and diastolic), heart rate (HR), and cutaneous temperature were measured. A set of visual analog scales, the 49-item short-form version of the Addiction Research Center Inventory (ARCI), and the Evaluation of the Subjective Effects of Substances with Abuse Potential (VESSPA-SSE) were used for the evaluation of subjective effects. OF was collected at baseline and at 10, 20, and 40 min and 1, 2, 3, and 4 h after self-administration. Statistically significant increases in systolic blood pressure (SBP), diastolic blood pressure (DBP), and HR were observed after JWH-122 self-administration but not after JWH-210 self-administration. JWH-210 self-administration produced significant changes in subjective drug effects, similar to those induced by THC (intensity, high, good effects, and hunger). The subjective effects following JWH-122 consumption were minimal. The maximal effects were mostly observed 20 min after intake. JWH-122 and JWH 210 OF concentration reached a peak 20 min after administration and could not be detected after 3 h. The results demonstrated a different pattern of effects of these two SCs. Due to the limitations of our observational study, further research with a larger sample and controlled studies are needed to better define the acute pharmacological effect and health risk profile of JWH-122 and JWH-210.

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A Japan nationwide web-based survey of patient preference for renal denervation for hypertension treatment

Hypertension Research ◽

10.1038/s41440-021-00760-9 ◽

2021 ◽

Author(s):

Kazuomi Kario ◽

Hideaki Kagitani ◽

Shoko Hayashi ◽

Satsuki Hanamura ◽

Keisuke Ozawa ◽

...

Keyword(s):

Blood Pressure ◽

Drug Therapy ◽

Side Effects ◽

Antihypertensive Drug ◽

Patient Preference ◽

Renal Denervation ◽

Antihypertensive Drugs ◽

Japanese Patients ◽

Home Blood Pressure ◽

Antihypertensive Drug Therapy

AbstractRenal denervation is a potential alternative to antihypertensive drug therapy. However, data on patient preference for this treatment option are limited and there are no data specifically from Asian patients. This study evaluated patient preference for renal denervation in patients with hypertension from Japan. Patients were a subset of those who participated in a March 2020 online electronic survey of patients with hypertension who had regularly visited medical institutions for treatment, were receiving antihypertensive drug therapy and had home blood pressure recordings available. The survey included a question about patient preference for treatment with renal denervation. A total of 2,392 patients were included (66% male, mean age 59.8 ± 11.6 years, mean duration of hypertension 11.4 ± 9.5 years). Preference for renal denervation was expressed by 755 patients (31.6%), and was higher in males than in females, in younger compared with older patients, in those with higher versus lower blood pressure, in patients who were less adherent versus more adherent to antihypertensive drug therapy, and in those who did rather than did not have antihypertensive drug-related side effects. Significant predictors of preference for renal denervation on logistic regression analysis were younger patient age, male sex, higher home or office systolic blood pressure, poor antihypertensive drug adherence, the presence of heart failure, and the presence of side effects during treatment with antihypertensive drugs. Overall, a relevant proportion of Japanese patients with hypertension expressed a preference for renal denervation. This should be taken into account when making shared decisions about antihypertensive drug therapy.

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Metabolic side effects of clozapine in patients at south ceredigion community mental health team

BJPsych Open ◽

10.1192/bjo.2021.905 ◽

2021 ◽

Vol 7 (S1) ◽

pp. S345-S345

Author(s):

Harish Reddy

Keyword(s):

Blood Pressure ◽

Metabolic Syndrome ◽

Side Effects ◽

Nutritional Intervention ◽

Serum Glucose ◽

Lifestyle Changes ◽

Glucose Levels ◽

Fasting Level ◽

Waist Size ◽

Patients At Risk

AimsThe aim of the audit was to identify patients at risk of developing Metabolic Syndrome who are on Clozapine in the community. Anyone who has three of following attributes has Metabolic Syndrome. A large waist size (greater than 40 inches in men or 35 inches in women) ,high blood pressure (130/85 mm Hg or higher) ,high triglycerides — a form of fat in the blood (150 mg/dL or higher) ,high blood sugar (a fasting level of 100 mg/dL or higher).Patients receiving should be regularly monitored under clinical review particularly in relation to side effects of the drug and maintain minimum standards of review both physically and clinical investigations once a year .BackgroundTo measure the screening of central obesity, Blood Pressure, serum glucose levels and lipid profile in last one year.MethodData were collected from Blood results and electronic entries of patients who are on Clozapine in South Ceredigion Community Mental Team. There were 31 patients of which 20 were male and 11 were female patients. The age range was 31–66 years and average was 46 years.Result52% of the patients had obesity,34 % with Hypertension,50 %Dyslipidaemia and 43 % had Increased glucose tolerance. 80 % were only on clozapine,3% were on combined Amisulpride, 10% on combined on Ariprazole, 3 % on combined Quetiapine.ConclusionTreatment of causes like making changing lifestyle changes, weigh reduction using health diet and to include regular physical activity. Reduce Abdominal Obesity and in possible provide nutritional intervention.

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