Although anti-hypertension therapies are the domain of primary care physicians, because of their widespread use they are common medications for hospital patients. Previous studies have shown that nocturnal anti-hypertensive dosing improves BP control, although have not addressed major cardiac outcomes.
This 10-year, large, multicenter RCT demonstrates benefit of evening medication dosing that has implications perioperatively.
The Hygia Project randomised 19,084 patients (x̄=61y 56%♂ 34%♀) to take their anti-hypertensive medications (≥1) either at bed-time or on awakening. Patients were followed for a median 6.3 years, routinely using 48h ambulatory BP monitoring at each follow-up review.
They found that...
Patients taking anti-hypertensives in the evening experienced better BP control and 45% lower rates of major cardiovascular outcomes, including CVD death, infarct, coronary revascularisation, heart failure and stroke.
Interestingly the progressive decline in sleeping SBP during the study was the strongest predictor of cardiovascular risk, stronger than traditional risk markers such as age, gender, DM, CKD, cholesterol or even smoking!
This is a significant finding from a large, high-quality study. It confirms the benefits of nocturnal dosing, also likely (though unconfirmed) to have intraoperative and perioperative benefits compared with morning dosing.
Why the fuss?
Acute renal injury is a common post-operative complication among high-risk patients and after major surgery, particularly cardiac and major vascular surgery, as is relevant to this study. The clinical relevance of ischaemic preconditioning continues to be controversial.
Even mild post-operative acute kidney injury (AKI) is associated with a wide range of poor perioperative outcomes, and current interventions have struggled to reduce such risk.
What is remote ischaemic preconditioning (RIPC)?
In an effort to protect an at-risk end organ from ischaemia (eg. heart, brain, kidneys), RIPC cyclically induces ischaemia in a remote site (typically an arm using an NIBP cuff). This activates physiological protective mechanisms against hypoxia and reperfusion injury in the target organ. It is cheap, easy and safe.
RIPC as a technique is based upon Murray’s 1986 observations of dog LAD arteries.
Although remote ischaemic (pre)conditioning has been demonstrated in animal models, human studies have been contradictory.
What was done...
This Shanghai research team randomised 130 patients undergoing open aortic arch replacement to receive either remote ischaemic preconditioning (4x 5-min-up 5-min-down) or sham preconditioning.
Fewer patients demonstrated renal injury at 7 days in the treatment group (55% vs 74%, ARR 95% CI 2-35%), in addition to shortening mechanical ventilation duration (18 vs 25 hours).
Practice changing? No
Although this study has shown a marked reduction in AKI in a uniquely very-high-risk group, as a sole small single-centered study it can barely be applied to the actual study population, let alone generalised to other high-risk groups.
Even when AKI in the control group was a massive 74%, the confidence interval for absolute risk reduction (2-35%) is so wide as to cast doubt on the credibility of this result.
Remote ischemic preconditioning reduced renal injury and mechanical ventilation duration, after open total aortic arch replacement.
Taking oral antihypertensive agents at bedtime rather than the morning, improves BP control and reduces the incidence of cardiac death, myocardial infarct, revascularization, heart failure and stroke.
Why is this relevant?
Sore throat following endotracheal intubation is common (reported in up to 68%), and along with postoperative nausea & vomiting, negatively impacts postoperative well-being.
Small studies have previously suggested that IV dexamethasone reduces sore throat due to intubation. It is thought this occurs by reducing mucosal inflammation at the point of tracheal cuff contact, the presumed aetiology of the majority of post-ETT sore throat.
Kuriyama and Maeda conducted a systematic review and meta-analysis of 15 RCTs totalling 1,849 patients.
And they found?
Preoperative dexamethasone IV (~4-10 mg across the studies) reduced the incidence of sore throat by almost 40% (RR 95% CI 0.51-0.75) and mean severity by 1.1 (SMD 95% CI 1.8-0.3).
Given the established effectiveness of preoperative dexamethasone to safely reduce post-operative nausea and vomiting, this meta-analysis affirms another important indication for the routine use of dexamethasone in intubated patients who do not have contraindications to steroid use.
Intravenous dexamethasone reduces the incidence and severity of sore throat after endotracheal intubation.
Low dose ketamine reduces pain and opioid requirements in the first 24 hours after major joint surgery.
Women are more satisfied with pain relief with labour epidural analgesia than with remifentanil PCA.
High level evidence does not show any clinically meaningful difference for early vs late labour epidural analgesia, whether on maternal or neonatal outcomes.
A greater relief in labor pain with epidural analgesia is associated with lower postpartum depression scores, although with less clinical significance than other risk factors.