quarta-feira, março 24, 2010
terça-feira, agosto 18, 2009
quinta-feira, maio 14, 2009
Nerve regeneration
domingo, maio 03, 2009
Mais links...
sábado, janeiro 31, 2009
Overdosing with Neuromuscular Blocking Drugs: a Universal Foible
Jennifer M. Hunter, MD
"What is it in the psyche of anesthesiologists that makes them use much more of a drug than is necessary to produce the desired effect? Is it simply a human failing or just laziness? Why is it that although the recommended dose of, for instance, atracurium is 0.5 mg/kg, so many anesthesiologists give at least 0.6–0.9 mg/kg at the beginning of anesthesia? Is it because they want a more rapid onset of action? Undoubtedly, it will be slightly faster, albeit only by a matter of seconds, with the larger dose. Do they want a longer clinical duration of action (25% recovery of the twitch response) of about 47 min after atracurium 0.9 mg/kg instead of 32 min after atracurium 0.6 mg/kg for any particular patient? I doubt it. It is "bucket anesthesia": rapidly and carelessly pouring an excessive, and inexact, amount of the requisite drug into a patient, as if to cover every eventuality, without any consideration of how long that dose is likely to produce a clinical effect. Do they give any thought to the variability of effect of a dose of any nondepolarizing drug given on a weight-related basis? Do they acknowledge that the standard deviation of 20% recovery (when an incremental dose can be given or reversal effected) from atracurium 0.5 mg/kg is 11 min, for a mean time of 43 min?1 How do they know that their patient is not at the upper end of that range of effect? They are probably relying on the spontaneous breakdown of the drug in the plasma by Hofmann degradation and ester hydrolysis. Remember the variable effect Katz showed in 1967 with tubocurarine 0.1 mg/kg. In 7% of patients, complete ablation of the four twitches of the train-of-four (TOF) response occurred, even with this very low dose.2
Only recently, it has been clearly demonstrated that all anesthesiologists use an unnecessarily large dose of succinylcholine.3 Succinylcholine 0.6 mg/kg will still have a rapid onset (81 s) and even 0.4 mg/kg may suffice, with maximum block at a mean of 105 s. More importantly, clinical recovery will be faster at 6.6 min after succinylcholine 0.4 mg/kg and 7.6 min after 0.6 mg/kg, compared with 9.3 min after succinylcholine 1.0 mg/kg.3 Thus, following preoxygenation, recovery of respiration could occur before hypoxic damage ensued if a smaller dose of succinylcholine had been used and intubation had failed. Even with succinylcholine, however, there is a range in the clinical recovery times of 5–6 min.3
The practice of using an excessive dose of muscle relaxant is made worse by the tendency to give a generous increment every 30 min ("on the half hour" in UK terminology). No thought is given to monitoring neuromuscular block to determine the degree of recovery prior to the increment. Nor is detection of the second twitch of the TOF response ascertained, as it should be, before another often excessive bolus is given, for instance, atracurium 15–20 mg.
It is not surprising that when surgery finishes somewhat earlier than expected, which occasionally happens, and an anticholinesterase such as neostigmine has been given, recovery from block is slow and incomplete, with all the potential complications that have been described.4 For if neostigmine 2.5 mg is given when the first twitch of the TOF response has recovered to 10% after vecuronium 0.1 mg/kg, it takes 3.9 min for T1/T0 to reach 70% and 9.2 min for the TOF ratio to reach 0.7, when the patient can probably be extubated safely. How many anesthesiologists wait 10 min after giving neostigmine before they extubate their patient? But if neostigmine 2.5 mg is not given until T1/T0= 0.5, it takes only 1.2 min for T1/T0 to reach 0.7, and only 2.1 min for the TOF ratio to do so.5
Anesthesiologists should realize that the art of their practice is to give a sufficient amount, but no more, of a neuromuscular blocking drug and its antagonist, and to give both drugs at an appropriate time. Only then will the desired effect of the drug be achieved and fewer side effects encountered. For instance, anesthesiologists do not want to produce unnecessary histamine release and subsequent hypotension from mivacurium by giving too large a dose (0.3 mg/kg) too rapidly, over 10–15 s.6 A 33% fall in mean arterial pressure can be anticipated in such circumstances. Nor do they wish to see the tachycardia and hypertension that result from administration of a large dose of that now archaic drug, pancuronium. Do they want an incomplete reversal when too much vecuronium has been given too frequently to a patient with either acute or chronic renal dysfunction?8 I see about three such cases a year in my hospital, so such occurrences must be common.
The tendency to encourage the use of larger doses of a nondepolarizing muscle relaxant, such as rocuronium 1.2 mg/kg or cisatracurium 0.4 mg/kg,8 to increase the rate of onset of block may at first seem attractive. But do not forget that prolonged neuromuscular block is then being produced. Twenty-five percent recovery of the first twitch of the TOF, when it is appropriate to give an anticholinesterase, takes 67 ± 25 (mean ± SD) min10 following rocuronium 1.2 mg/kg and 91 ± 3.3 (mean ± SE) min after cisatracurium 0.4 mg/kg.8 Few anesthesiologists appreciate the length of action of the neuromuscular blocking drugs they use.
Never forget the old days of recurarization. This phenomenon should no longer occur except in patients with undiagnosed neuromuscular disorders such as myasthenia gravis and amyotrophic lateral sclerosis, or in the hypothyroid patient. It could be considered a sign of negligence for a patient to experience residual curarization in the recovery room. For now there are drugs that are broken down independent of organ function, such as atracurium, cisatracurium, and mivacurium. If the correct dose of these drugs is used, neuromuscular block is monitored, and the anticholinesterase is given only when the second twitch of the TOF response is detectable; then residual block should never be seen. In the days of tubocurarine and pancuronium, it was more understandable if patients had impaired clearance of these long-acting drugs from reduced renal or hepatic function (which can occur in the hypovolemic shocked patient as well as in the patient with chronic organ dysfunction).
Remember too that organ function deteriorates with increasing age. The older the patient, the lower the rate of clearance and the longer the elimination half time of a neuromuscular blocking drug, even if it primarily undergoes organ-independent elimination. How many anesthesiologists consider the age of their patients before selecting the dose of a neuromuscular blocking drug? It is inappropriate to use the same dose in a 20-year-old patient as in an 80-year-old patient, even if they are of the same sex and weight. If succinylcholine is given to intubate a patient, the duration of action of the nondepolarizing agent will also be potentiated.
The clearance of many nondepolarizing neuromuscular blocking drugs is lower in women, so they may need a smaller dose to achieve an effect similar to that in men.9 Ethnicity is also important; different races metabolize drugs at different rates. This difference is augmented by the different rates of alcohol consumption and cigarette smoking in different cultures, as these substances stimulate hepatic enzyme induction and faster metabolism of drugs cleared by the liver. Thus the nonsmoking, non–alcohol-consuming, nonwhite, vegetarian lady will be more sensitive to the effect of a neuromuscular blocking drug than an overweight white man who smokes and who drinks a large amount of alcohol every day. In addition, it is uncertain whether in adults it is necessary to give a dose of neuromuscular blocking drugs such as atracurium, which undergo organ-independent elimination on a weight-related basis. Atracurium 25 mg will be sufficient in most adult females, and atracurium 30 mg in adult males.
So remember, there is no rationale for using excessive doses of neuromuscular blocking drugs. By taking pride in giving a good anesthetic in which the dose of all drugs used is tailored to a particular patient, anesthesiologists can achieve an ideal effect, for both the well-being of their patients and the smooth running of their practice."
"Right conduct can never, except by some rare accident, be promoted by ignorance or hindered by knowledge"(Bertram Russell, 1929).1. Hunter JM, Jones RS, Utting JE: Comparison of vecuronium, atracurium and tubocurarine in normal patients and in patients with no renal function. Br J Anaesth 1984;56:941. [PMID: 6147153] |
| 2. Katz RL: Neuromuscular effects of d-tubocurarine, edrophonium and neostigmine in man. Anesthesiology 1967;28: 327. |
| 3. Kopman AF, Zhaku B, Laik S: The intubating dose of succinylcholine: The effect of decreasing doses on recovery time. Anesthesiology 2003;99:1050. [PMID: 14576537] |
| 4. Savarese JJ: A current practice of relaxation. In: Clinical Anesthesiology, 3rd ed. McGraw-Hill, 2002 (Chapter 9). |
| 5. Jones JE, Hunter JM, Utting JE: Use of neostigmine in the antagonism of residual neuromuscular blockade produced by vecuronium. Br J Anaesth 1987;59:1454. [PMID: 2891365] |
| 6. Savarese JJ, Ali HH, Basta SJ, et al: The cardiovascular effects of mivacurium chloride (BW B1090U) in patients receiving nitrous oxide–opiate-barbiturate anesthesia. Anesthesiology 1989;70:386. [PMID: 2564261] |
| 7. Cody MW, Dormon FM: Recurarization after vecuronium in a patient with renal failure. Anaesthesia 1987;42:993. [PMID: 2890315] |
| 8. Belmont MR, Lien CA, Quessy S, et al: The clinical neuromuscular pharmacology of 51W89 in patients receiving nitrous oxide/opioid/barbiturate anesthesia. Anesthesiology 1995;82:1139. [PMID: 7741288] |
| 9. Parker CJR, Hunter JM, Snowdon SL: Effect of age, sex and anaesthetic technique on the pharmacokinetics of atracurium. Br J Anaesth 1992;69:439. [PMID: 1467071] |
sexta-feira, dezembro 26, 2008
sexta-feira, outubro 24, 2008
segunda-feira, outubro 13, 2008
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."
sábado, outubro 11, 2008
Bicarbonato de sódio...
- 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.
sexta-feira, outubro 03, 2008
Manobra de Valsava
"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
sexta-feira, junho 13, 2008
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.
quarta-feira, dezembro 19, 2007
"Anaesthetists Hymn LIVE" ...ou o Hino da Anestesia!
Encontrei este vídeo por sugestão da Marlene... sarcástico!!
BOM NATAL E BOM 2008!
P.S.: Quem quiser ser (re)invited para postar no blog (re)enviem mail para internatoanestesiahgsa@gmail.com
segunda-feira, dezembro 17, 2007
a cura para todos os males
- Para ver e ouvir com cuidado, que a informação contida neste filme tem que se lhe diga... -
(PS: Eu sei que o blog está praticamente morto, mas que querem?!)
sábado, setembro 15, 2007
Stents metálicos - segundo fôlego?
Entre o que vi, acho que este endereço (e os respectivos links), é um bom ponto de partida para quem estiver interessado e não tiver passwords para aceder às respectivas revistas..
http://www.heartzine.com/511-Heart-No-Better-Off-With-Drug-Eluting-Stents.html
Cumprimentos
MSP
