Boas Festas...

Em jeito de prenda de Natal, estes dois...

Hino dos Anestesistas - Clip

Apresentado pelo Francisco Lobo na última reunião de internos...

Higiene no Bloco...

A propósito de lavagem das mãos no Bloco...

Liver explosion!

Featured images from Trauma.org (>>>>vide links>>>>)

"Luis Filipe Pinheiro Hospital S. Teotónio - VISEU PORTUGAL

This patient has sustained a gunshot wound in the LUQ. Transfered imediately to the OR, a xiphopuibic laparotomy with extention to the RUQ was done. He had a blasted liver (Grade V lesion) as the only intrabdominal lesion. No other visceral injuries! The patient died on table from exanguination."

Bicarbonato de sódio...

A propósito de uma conversa que tive com a Jacinta na nossa última urgência sobre a administração de bicarbonato de sódio a doentes com acidose láctica, fica o resumo de um artigo de revisão sobre o assunto.

O artigo apresenta e analisa criticamente resultados de vários estudos experimentais e clínicos e está dividido nas seguintes áreas:

• Is a low pH bad?
• Can sodium bicarbonate raise the pH in vivo?
• Does increasing the blood pH with sodium bicarbonate have any salutary effects?
• Does sodium bicarbonate have negative side effects?

Sodium bicarbonate is clearly effective in raising the arterial pH in critically ill patients with lactic acidosis. The impact on intracellular pH is unknown in such patients, but extrapolation from extensive animal studies suggests that it is negative.

Despite the correction of arterial acidemia, sodium bicarbonate, like DCA, has no favorable cardiovascular effects, even for patients with severe acidemia and receiving continuous infusions of catecholamines. Although hemodynamic improvement is not the only mechanism by which bicarbonate might be beneficial, animal studies have failed to yield alternatives.

Even theoretical arguments in favor of sodium bicarbonate administration rely on a naive representation of acid-base physiology, ignoring the complex compartmentalization of pH, the second-level effects of bicarbonate infusion, the impact of carbon dioxide generation, or the negative consequences of hyperlactatemia.

We believe most clinicians who continue to use bicarbonate for patients with severe lactic acidosis do so largely because of their inclination to action: How can I “fail” to give bicarbonate when no alternative therapy is available and the mortality of this condition is so high? The oft-cited rationale for bicarbonate use, that it might ameliorate the hemodynamic depression of metabolic acidemia, has been disproved convincingly.

Any future role for bicarbonate in these patients depends on the formulation of new hypotheses of efficacy followed by animal and clinical studies to seek to confirm any proposed benefit. Given the current lack of evidence supporting its use, we cannot condone bicarbonate administration for patients with lactic acidosis. We extend this to those with pH , 7.2 on vasoactive drugs, inasmuch as bicarbonate has no measurable beneficial effects even in these sickest patients. Indeed, we do not give or advise bicarbonate infusion regardless of the pH.

Fonte: Forsythe SM, Schmidt GA: Sodium Bicarbonate for the Treatment of Lactic Acidosis. CHEST 2000; 117:260–267.

Manobra de Valsava

Em relação a uma discussão que foi levantada pela Teresa Leal sobre a manobra de Valsava (pergunta 61 da pág. 120 "The primary FRCA, A complete guide to preparation and passing"):


"Forced expiration against a closed glottis after a full inspiration.

Standardised form 40 mmHg held for 10 seconds

Previously used to expel pus from the middle ear.

[Antonio Valsava (1666-1723), Italian anatomist].





Phase I
Blood is expelled from the thoracic vessels by the increase in intrathoracic pressure.

Phase II
The increase in intrathoracic pressure causes a reduction of venous return, lowering the preload and BP

The baroreceptor reflex is activated, causing vasoconstriction and a tachycardia, raising BP towards normal.

Phase III
As intrathoracic pressure suddenly drops there is pooling of blood in the pulmonary vessels, causing a further drop in BP.

Phase IV
With venous return restored there is an overshoot, as compensatory mechanisms continue to operate.

The increased BP causes a baroreceptor mediated bradycardia.

The Valsalva manoeuvre is a useful bedside test of autonomic function. With autonomic dysfunction (e.g. autonomic neuropathy and drugs), the BP falls and remains low until the intrathoracic pressure is released. The changes in pulse rate and overshoot are absent. For reasons that are still obscure, patients with primary hyperaldosteronism also fail to show the heart rate changes and the blood pressure rise when the intrathoracic pressure returns to normal. Their response to the Valsalva manoeuvre returns to normal after removal of the aldosterone-secreting tumour.

Other abnormal responses

Square wave response
Seen in cardiac failure, constrictive pericarditis, cardiac tamponade and valvular heart disease. Blood pressure rises, remains high throughout the manoeuvre, and returns to its previous level at the end





Figure 2. Arterial blood pressure response and Korotkoff's sounds during Valsalva's manoeuvre.

(A) Sinusoidal response in normal patient.

(B) Absent overshoot in patient with autonomic dysfunction.

(C) Square wave response in patient with heart failure"



from AnesthesiaUK

Learning from Aprotinin — Mandatory Trials of Comparative Efficacy and Safety Needed

Na sequência da discussão surgida na RE (13.06.2008) e do email da DC aconselho a ler este editorial a propósito da saga da aprotinina.

EDITORIAL de Ray, Wayne no NEJM (Vol. 358 de 21 de Fevereiro de 2008)

Learning from Aprotinin — Mandatory Trials of Comparative Efficacy and Safety Needed

Aprotinin, a hemostatic agent that inhibits the fibrinolytic enzyme plasmin,1 was approved by the Food and Drug Administration (FDA) in 1993 for reducing blood loss during coronary-artery bypass grafting (CABG). By 2006, aprotinin was prescribed for approximately 200,000 patients undergoing cardiac surgery worldwide.2 Aminocaproic acid and tranexamic acid are lysine analogues that inhibit the binding of fibrin to plasminogen and also reduce blood loss, but a specific indication for bypass grafting is not included on their labels.1 The safety of aprotinin was called into question in 2006 and 2007, when the results of an international cohort study by Mangano et al. of patients undergoing CABG were published. The findings included increased risks of renal failure, myocardial infarction, and stroke and increased 5-year mortality with aprotinin but not with the lysine analogues.2,3 Two additional cohort studies in this issue of the Journal show that patients undergoing CABG who received aprotinin had greater mortality — in the short term, as reported by Schneeweiss et al.,4 and in the long term, as reported by Shaw et al.5 — than did those who received aminocaproic acid.

In October 2007, the data and safety monitoring board stopped the enrollment of patients into a large Canadian study of the use of aprotinin, as compared with aminocaproic acid or tranexamic acid, during cardiac surgery (Blood Conservation using Antifibrinolytics: A Randomized Trial in a Cardiac Surgery Population [BART]; ISRCTN no. 15166455).6 An interim analysis of more than 2000 patients found increased 30-day mortality in the aprotinin group. Subsequently, the manufacturer temporarily suspended the worldwide marketing of aprotinin, pending a full review of the trial data, thus limiting its use to that by physicians participating in a restricted, special-access protocol. Although the findings from BART, which included patients undergoing both CABG and valve surgery, are preliminary and are reported to have borderline statistical significance, the future for aprotinin now appears very cloudy. The recommendation of the data and safety monitoring board to halt BART, coupled with the increased mortality associated with aprotinin use in three independent cohort studies, will make it difficult, in the absence of convincing new data, to prescribe this drug, except perhaps in limited circumstances.

What can we learn from the saga of aprotinin, a drug that apparently confers less overall benefit than cheaper alternatives yet has remained on the market for more than 14 years and become the recommended hemostatic agent for high-risk cardiac surgeries?1 Aprotinin was approved for cardiac surgery on the basis of premarketing randomized, controlled trials that showed reduced blood loss with aprotinin as compared with placebo. Even around the time of its introduction, concerns were raised about adverse prothrombotic and renal effects, and some experts suggested that aminocaproic acid was a better therapeutic choice.7 Nevertheless, there was no requirement for more definitive information on infrequent but serious complications, survival after surgery, and performance relative to then-available alternatives. The lack of critical clinical information about newly licensed medications reflects the balancing of the need for these data against the need for timely drug availability.8

The safety of aprotinin ultimately was challenged by the results of observational studies, in which routine clinical practice determines the therapy patients receive. Despite sophisticated statistical techniques used to compensate for potential imbalances among treatment groups, there is always concern that unmeasured factors bias the results. Indeed, many thought that the findings of Mangano et al. reflected this type of confounding.9,10 Aprotinin clearly reduced the need for blood transfusions 1 and thus was more likely to be prescribed for patients with greater anticipated perioperative blood loss. An increased risk of adverse events would be expected for these higher-risk cases, which the investigators' data might not have identified as such. The studies of Schneeweiss et al. and Shaw et al. reinforce this concern: the cases in which aprotinin was given were more complicated than those in which another (or no) agent was given, and the relative-risk estimates decreased after adjustment for measured covariates. Although the instrumental-variable analysis by Schneeweiss et al. allays some of these concerns, the study was also observational and thus potentially susceptible to bias from unmeasured characteristics associated with surgeons' preference for aprotinin.

The conclusion that confounding influenced the findings of Mangano et al. was buttressed by meta-analyses of numerous, relatively small randomized, controlled trials. A pooled analysis of the clinical-trial database of the manufacturer of aprotinin found no significantly increased risk of renal failure, myocardial infarction, stroke, or death from any cause for aprotinin users. This apparently played an important role in the recommendation by the Cardiovascular and Renal Drugs Advisory Committee of the FDA not to require additional warnings on the label for aprotinin.9 A Cochrane Collaboration meta-analysis of data from 211 randomized, controlled trials involving a total of 20,781 patients had similar findings.11

The apparent discrepancy between BART and the meta-analyses highlights the insufficiently appreciated pitfalls of pooling data from many small trials to establish drug safety.12 Meta-analyses of end points that the original trials were not designed or powered to study have methodologic limitations that may obscure safety problems. These limitations include the heterogeneity of patient populations and surgical procedures, the short duration of follow-up, and limited or incomplete information on the end points. In the Cochrane analysis of blood transfusion in 98 trials of aprotinin with no alternative hemostatic agent,11 mortality data were reported in only 52. Even fewer aprotinin trials had mortality data for the crucial comparisons with the lysine analogues: 14 trials for tranexamic acid and 3 trials for aminocaproic acid.

The history of aprotinin thus exemplifies the intrinsic limitations of current approaches to evaluation of the comparative efficacy and safety of new medications. Premarketing testing leaves many important questions unanswered because of the frequent reliance on comparison with placebo and the limited numbers of patients studied.8 Although observational studies provide the opportunity to conduct comparative studies of large numbers of patients, the aprotinin story shows how concerns about residual bias limit the utility of nonrandomized studies — concerns that are reinforced by high-profile discrepancies between observational studies and randomized, controlled trials. Meta-analyses of randomized, controlled trials have many limitations that may bias the results toward showing no difference between the treatment groups for end points the original trials were not designed to study. The coxibs are another case in point. Meta-analyses that compared these drugs with placebo reported no increased risk of serioius cardiovascular disease, whereas subsequent large, randomized, controlled trials found that such risk was increased by a factor of 2 to 3.13,14

Thus, the key lesson from the aprotinin story is that when a new drug has alternatives, as is the case for aprotinin, head-to-head comparative trials powered for important clinical end points are needed before the drug is routinely prescribed for large numbers of patients.8 These randomized trials are the best way to define relative efficacy and safety, the most critical information for patients and physicians. If, as is often the case, these trials are not part of the premarketing testing, then they should be conducted as soon as possible after licensing. The manufacturer cannot be relied on to perform these studies voluntarily, because they frequently serve no commercial purpose. Indeed, several observers noted the dearth of trials comparing aprotinin with the lysine analogues 1,10,11 and commented on the economic disincentives for direct comparisons of competing therapies.10 Thus, when indicated, postmarketing comparative efficacy and safety trials, supervised by the FDA, should be mandatory.8 To limit the risk for patients, distribution of new drugs should be restricted while these trials are being conducted, with selective extension of patents to reduce the economic burden on the manufacturer.8,15

The FDA Amendments Act of 2007 gives the agency new authority to require postmarketing studies and to place restrictions on drug distribution or use.16 Thus, depending on how the regulations for this legislation are written and interpreted, this reform may facilitate comparative efficacy and safety trials and allow for the phased release of new drugs. If it ultimately does not, the legislation should be amended appropriately. Otherwise, we will continue to repeat the unfortunate history of aprotinin, in which large numbers of patients received a therapy that apparently was suboptimal.