FDA Press Release, 10/20/08

The Hartz Mountain Corporation Voluntarily Recalls One Specific Lot of Nationwide Chicken-Basted Rawhide Chips Because of Possible Health Risk

Contact:
John Mullane
(914) 712 9150

FOR IMMEDIATE RELEASE — October 20, 2008 — The Hartz Mountain Corporation, Secaucus, NJ is voluntarily recalling one specific lot of Hartz Chicken-Basted Rawhide Chips due to concerns that one or more bags within the lot are potentially contaminated with Salmonella. Hartz is fully cooperating with the US Food and Drug Administration in this voluntary recall.

Salmonella can cause serious infections in dogs, and, if there is cross-contamination caused by handling of the rawhide chips, in people as well, especially children, the aged, and people with compromised immune systems. Healthy people potentially infected with Salmonella should monitor themselves for some or all of the following symptoms: nausea, vomiting, diarrhea or bloody diarrhea, abdominal cramping and fever. On rare occasions, Salmonella can result in more serious ailments, including arterial infections, endocarditis, arthritis, muscle pain, eye irritation, and urinary tract symptoms. Consumers exhibiting these signs after having contact with this product should contact their healthcare providers.

Pets with Salmonella infections may be lethargic and have diarrhea or bloody diarrhea, fever, and vomiting. Some pets will have only decreased appetite, fever and abdominal pain. Animals can be carriers with no visible symptoms and can potentially infect other animals or humans. If your pet has consumed the recalled product and has these symptoms, please contact your veterinarian.

The product involved is 4,850 – 2 pound plastic bags of Hartz Chicken-Basted Rawhide Chips, lot code JC23282, UPC number 3270096463 which were distributed to a national retail customer. While the normal testing that Hartz conducts through an independent outside laboratory did not detect the presence of Salmonella in any Hartz rawhide products, sample testing conducted by another laboratory did indicate the presence of the bacteria in a sample bag of the Chicken-Basted Rawhide Chips. Hartz is aggressively investigating the difference in test results and the potential source of the problem.

Although Hartz has not received any reports of animals or humans becoming ill as a result of coming into contact with this product, Hartz is taking immediate steps to remove the product from all retail stores and distribution centers. Dog owners who purchased this product should check the lot code on their bag, and, if the code is not visible, or if the bag has lot code JC23282 imprinted thereon, they should immediately discontinue use of the product and discard it in a proper manner.

Consumers can contact Hartz at 1-800-275-1414 with any questions they may have and to obtain reimbursement for purchased product.

Source:  http://www.medscape.com/viewarticle/578393?sssdmh=dm1.395711&src=journalnl

From The Annals of Pharmacotherapy

TITLE:  2007 Guideline Update for Unstable Angina/Non-ST-Segment Elevation Myocardial Infarction: Focus on Antiplatelet and Anticoagulant Therapies

Posted 08/26/2008 (Full Text: http://www.medscape.com/viewarticle/578393?sssdmh=dm1.395711&src=journalnl)

James C Coons, PharmD BCPS; Sarah Battistone, PharmD

Abstract

Objective: To summarize key changes in the 2007 American College of Cardiology/American Heart Association (ACC/AHA) guideline recommendations for pharmacologic therapy as they relate to antiplatelets and anticoagulants, and to evaluate the evidence from several landmark trials that was used to support the guideline updates for these agents.
Data Sources: Literature was accessed through MEDLINE (1950–January 2008) using the search terms acute coronary syndromes, unstable angina (UA), non–ST-segment elevation myocardial infarction (NSTEMI), antiplatelet, and anticoagulant. All papers were cross-referenced to identify additional studies.
Study Selection and Data Extraction: ACC/AHA guidelines, relevant original research articles, and review articles were evaluated. Studies with more than 1000 patients were the focus of the review.
Data Synthesis: UA and NSTEMI are the most common presentations of acute coronary syndrome. The recently updated ACC/AHA guidelines for management of this condition were based on significant advances in pharmacotherapy including expanded use of drug-eluting stents, pretreatment with clopidogrel, and newer anticoagulants such as bivalirudin and fondaparinux. Landmark trials have been published that describe advances in the use of antiplatelets and anticoagulants. According to the guidelines, unfractionated heparin (UFH) and enoxaparin are preferred options for both invasive and conservative management. Enoxaparin was noninferior to UFH for invasive management in the SYNERGY trial, although it was associated with a higher incidence of bleeding. Other alternatives for an invasive strategy per the guidelines include bivalirudin and fondaparinux. Bivalirudin (alone or with glycoprotein [GP] IIb/IIIa inhibitor) was compared with heparin plus GP IIb/IIIa inhibitor in the ACUITY trial of patients undergoing early invasive management. The bivalirudin groups were noninferior to standard of care, although bivalirudin alone was associated with less bleeding. Fondaparinux was found to be noninferior to enoxaparin and was associated with fewer bleeding events in the OASIS-5 study of patients who were not treated with an early invasive approach. Accordingly, the guidelines 1list fondaparinux as an alternative for a conservative strategy or in patients at increased risk of bleeding.
Conclusions: Clinicians should be familiar with the updated 2007 ACC/AHA guidelines and the clinical trial evidence that serves as the basis for these recommendations. It is paramount for institutions to outline a preferred and consistent treatment approach. These decisions should involve a review of established efficacy, bleeding risk, need for anticoagulant reversal, costs, and clinician familiarity with different treatment regimens.
 

Source:

From Continuting Education in Anaesthesia, Critical Care & Pain

Management of Life-Threatening Asthma in Adults

Posted 09/03/2008 (http://www.medscape.com/viewarticle/578690?sssdmh=dm1.395711&src=journalnl)

Authors:  David Stanley, MRCP, FRCA; William Tunnicliffe, FRCP
   

Initial Management

A rapid ABC assessment should be undertaken and actioned. Many patients will be hypoxaemic, hypovolaemic, acidotic, and hypokalaemic.

Oxygen. Patients with acute severe asthma are hypoxaemic. This should be corrected urgently with high concentrations of inspired oxygen aiming to achieve oxygen saturations >92%. A Fi_O2 of 0.4-0.6 is often sufficient but, in general, start high and then titrate the Fi_O2 down. It is important to note that asphyxia remains the most common mechanism of death in severe asthma and should never be underestimated.

Nebulized β₂ Agonists. Short-acting β₂-agonists (e.g. salbutamol) should be given repeatedly in 5 mg doses or by continuous nebulization at 10 mg h^-1 driven by oxygen. Importantly, duration of activity and effectiveness are inversely related to severity of asthma; continuous administration is more efficacious in severe asthma. However, even under ideal circumstances only 10% of the nebulized drug will reach the bronchioles.^[2] Administration should continue until there is a significant clinical response or serious side effects occur, these include tachycardia, arrhythmias, tremor, hypokalaemia, and hyperglycaemia. Inhaled longer acting β₂-agonists have no role in management of acute severe asthma and may increase mortality in this setting.

Nebulized Ipratropium Bromide. This should be added to nebulized β₂ agonists treatment for all patients with life-threatening asthma (500 µg 4 hourly) as it has been shown to produce significantly greater bronchodilation than β₂ agonists alone. Side effects are minimal.

Steroids. Systemic steroids in adequate doses should be given to all patients with life-threatening asthma, as early as possible in the episode as this may improve survival. Steroid tablets (prednisolone 40-50 mg daily) have been shown to be as efficacious as intravenous steroids in acute severe asthma, provided tablets can be swallowed and retained. If in any doubt, the intravenous route should be used (hydrocortisone 200 mg stat followed by 100 mg 6 hourly). Inhaled/nebulized steroids do not provide additional benefit.

Intravenous Magnesium Sulphate. A single intravenous dose of magnesium sulphate 1.2-2 g over 20 min has been shown to be safe and effective in acute severe asthma. Magnesium is a smooth muscle relaxant, producing bronchodilation. Rapid administration may be associated with hypotension. Anecdotal evidence suggests repeated doses or infusions may be of benefit (dose limited by twice normal serum magnesium concentrations); however, hypermagnesaemia is associated with muscle weakness and may exacerbate respiratory failure in spontaneously breathing patients.

Intravenous Bronchodilators. Parenteral β₂ agonists, in addition to nebulized β₂ agonists, should be considered in ventilated patients and those with life-threatening asthma; intravenous salbutamol (5-20 µg min^-1) or terbutaline (0.05 µg kg^-1 min^-1) should be titrated to response. Lactic acidosis will develop in 70% of patients after 2-4 h therapy, requiring careful monitoring with subsequent reduction or cessation of therapy. In extremis, salbutamol 100-300 µg can be given as an intravenous bolus or via an endotracheal tube.

An additional or alternative intravenous bronchodilator is aminophylline. Some patients with life-threatening asthma gain benefit from its intravenous use (5 mg kg^-1 loading dose over 20 min unless on maintenance oral therapy, then infusion of 0.5-0.75 mg kg^-1 min^-1). Concern and controversy about its use arises from its side effects (arrhythmias, restlessness, vomiting, and convulsions) related to a narrow therapeutic window. Trials showing little overall benefit in lesser degrees of asthma may not be relevant when faced with impending asphyxia. Plasma aminophylline concentrations should be monitored frequently (therapeutic range 10-20 µg ml^-1).

Epinephrine. The additional use of epinephrine (adrenaline) should be considered in patients not responding adequately to the measures outlined above via the subcutaneous (0.3-0.4 ml 1:1000 every 20 min for three doses), nebulized (2-4 ml of 1% solution hourly) or, in extremis, the intravenous route (0.2-1 mg as a bolus followed by 1-20 µg min^-1).

Mechanical Ventilation

Who Should Be Intubated, and When and How Should Mechanical Ventilation Be Initiated? The initiation of invasive ventilation in life-threatening asthma is a bedside clinical decision based on an assessment of the balance of risks and benefits. It can be life saving, but has a higher incidence of complications relative to other causes of respiratory failure. Absolute indications are coma, respiratory or cardiac arrest and severe refractory hypoxaemia. Relative indications include an adverse trajectory of response to initial management, fatigue and somnolence, cardiovascular compromise, and the development of a pneumothorax. Prior to initiation, vigilant observation is mandatory as fatal apnoea can occur suddenly and unexpectedly.^[3] Hypercapnia per se is not an indication for mechanical ventilation.

In life-threatening asthma, the induction of anaesthesia, tracheal intubation, and initial ventilation are all extremely hazardous as dramatic changes in physiology occur with the induction of anaesthesia, and with the switch from high intrinsically produced negative intrathoracic pressures to high positive pressures from extrinsic ventilation. Half of the life-threatening complications occur at or around the time of intubation in patients mechanically ventilated for asthma; consequently, intubation should be performed by the most senior and experienced member of anaesthetic staff available with the help of appropriately trained assistance. Where possible, pre-oxygenation should be performed diligently followed by a rapid sequence induction. Hypotension at the initiation of ventilation should be anticipated and attenuated by fluid pre-loading. Vasopressors should be immediately available for use post-induction. Hypotension can be severe enough to result in complete loss of cardiac output or mimic that occurring with a tension pneumothorax. Causes of hypotension are multifactorial, including vasodilatation and reduction in sympathetic tone on induction, absolute hypovolaemia and reduction in venous return consequent to high intrathoracic pressures precipitated by ventilating against high airway resistance. Initial hand ventilation is often over-enthusiastic and contributory; it should follow the principles outlined for the mechanical ventilation below and be kept to a minimum; rate should be kept low and no PEEP should be applied. If profound hypotension does occur when assisted ventilation has been initiated, consideration should be given to disconnecting the patient from the circuit (possibly with the addition of pressure on the chest wall to assist expiratory flow) to allow full passive expiration A chest x-ray should be performed following intubation when it is safe to do so, to assess correct positioning of the endotracheal tube and exclude pneumothoraces.

What Are the Initial Goals of Mechanical Ventilation and How Are They Achieved? The initial goals of mechanical ventilation are to correct hypoxaemia, reduce dynamic hyperinflation and to buy time for medical management to work.

Adequate sedation is vital and typically would be morphine and midazolam with ketamine. Morphine has a potential for histamine release so is avoided by some. Propofol and fentanyl, and ketamine plus midazolam alone are alternatives. The attraction of ketamine (0.5-2 mg kg^-1 h^-1) is its action as a direct bronchodilator. Evidence of benefit is equivocal; use maybe limited by its effects on respiratory tract secretions and its sympathomimetic properties in a patient already in a heightened sympathetic state.

Initial neuromuscular blockade is often required. Rocuronium or pancuronium is the agents of choice. Atracurium is associated with histamine release. Some concern has been raised over the relative likelihood of developing a neuromyopathy with vecuronium in this setting (high-dose steroids, mechanical ventilation, and severe asthma), though the evidence is limited. The use of neuromuscular blockade should be discontinued as soon as possible.

Initial ventilator settings should adopt relatively low rates (12-14 breaths min^-1), tidal volumes of 4-8 ml kg^-1, Fi_O2 sufficient to maintain adequate oxygen saturations (>92%), relatively long-expiratory times (I:E 1:4) and little or no PEEP (<5 cm H₂O). If using volume controlled ventilation, appropriate goals would be to achieve a P_plat <35 cm H₂O with pH > 7.2. If P_plat > 35 cm H₂O, minute ventilation should be reduced (V_t and/or rate), if pH < 7.2 and P_plat < 30 cm H₂O, minute ventilation should be increased (rate), if pH < 7.2 and P_plat > 35 cm H₂O no change may be appropriate. This guidance principally derives from Tuxen and Lane’s^[7] observations of volume controlled ventilation in asthma, namely that minute ventilation is the most important determinant of hyperinflation (inspiratory flow and shape of pressure wave-form being of much lesser importance), and that while increased-expiratory times are beneficial, the effect of increases above 3-4 s are minimal. In addition, the role of PEEPe to counter PEEPi in controlled mechanical ventilation has no rationale, although recently potentially beneficial effects of PEEPe have been reported in ‘obstructive lung disease’ (as opposed to asthma) suggesting that a trial of variable PEEPe may be required in some cases.^[5]

Achieving the goals of a pH > 7.2 with a P_plat < 35 cm H₂O will often not be possible and requires ongoing clinical assessment. High airway pressures should prompt the exclusion of endobronchial intubation and pneumothorax, along with the re-evaluation of the adequacy of sedation.

Plateau airway and end-expiratory pressures generally reflect the degree of gas trapping in severe asthma; in addition, total exhaled volume during an apnoea for 20-60s gives a measure of the degree of hyperinflation.^[6] Not all airways remain patent throughout expiration, any measurement will tend to be an underestimate and clinical assessment remains vital. Of note, barotrauma in the mechanically ventilated asthmatic including the risk of pneumothorax is proportional to end inspiratory lung volume.

Additional complications of mechanical ventilation in life-threatening asthma include profound hypotension, cardiac stunning, arrhythmia, rhabdomyolysis, lactic acidosis, myopathy, and CNS injury. Cardiac stunning is thought to be consequent to massive sympathetic activation, arrhythmias generally tend to be benign, rhabdomyolysis is rare and is thought to stem from hypoxaemia in combination with extreme exertion; lactic acidosis in severe asthma is poorly understood.

Management of Hypercarbia. Permissive hypercapnia is a well-proven protective lung strategy for limiting the deleterious effects of barotrauma in many causes of respiratory failure. During the mechanical ventilation for life-threatening asthma, our ability to correct hypercapnia is generally limited and fraught with hazards. Although calling it ‘permissive’ might be a misnomer, hypercapnia is generally well tolerated, and there are numerous case reports in the literature of asthmatic patients with profound respiratory acidosis of several hours duration with no significant adverse effects. The exception is in those with cerebral anoxia secondary to a respiratory arrest. Control of intracranial pressure requires management of hypercarbia; urgent consideration should be given to extra corporeal CO₂ removal in these circumstances (see later).

Where respiratory acidosis is extreme and its ventilatory management impossible, buffering can be considered acutely. Tromethamine (THAM) has some theoretical advantages over bicarbonate. Use with either agent is usually complicated by metabolic alkalosis on resolution of the acute bronchospastic episode. Measures to limit CO₂ production, such as anti-pyretics and/or active cooling, should be considered as adjuncts or alternatives.

Ongoing Ventilatory Management. The use of neuromuscular blockade and deep sedation should be discontinued as soon as the clinical situation allows and the return to spontaneous ventilation should be achieved as soon as is practical. During this process, patient ventilator interactions become more important and the use of PEEPe and the selection of appropriate trigger sensitivities assume important roles in reducing the work of breathing.

The ventilator care bundle approach should be considered and, if not already involved, advice from a respiratory physician should be sought with a view to planning the patient’s ongoing management in hospital and in the community.

Additional Management Methods

Inhalational Anaesthetic Agents. Volatile inhalational anaesthetic agents (e.g. isoflurane and sevoflurane) are effective bronchodilators and their use is associated with reductions in PEEPi and Pa_co2 within hours. Increased benefit may occur with earlier administration and their use should be considered in patients with life-threatening asthma not responding to standard treatments. Hypotension is their principal side effect. The delivery of volatile anaesthetic agents can be difficult in the intensive care unit setting and may force the use of a lower fidelity ventilator in a sub-optimal environment. In line devices for use with high fidelity ventilators are available, but scavenging and agent monitoring are absolute requirements.

Extra-corporeal Support. Case reports of the use of extra-corporeal membrane oxygenation in life-threatening asthma suggest that this may be successful, but its limited availability and the risk profile limit its applicability. In contrast, the development of less complex systems of extra-pulmonary gas exchange that facilitate CO₂ clearance (e.g. Novalung) brings extra-corporeal CO₂ removal (ECCO₂R) within bounds. Their use should be considered particularly where the control of hypercarbia is imperative.

Bronchoscopy. Bronchoscopy has a limited role in managing patients with persistent shunt consequent to mucus plugging. Lavage of the obstructed lung segments and the removal of mucus plugs may reduce the duration of ventilation, but is often complicated by bronchospasm. In general, patience and persistence with standard therapies and meticulous attention to the hydration and humidification are as effective.

Antibiotics. The majority of episodes of acute severe asthma that has an infective precipitant follow a viral infection. The routine use of antibiotics in life-threatening asthma has no rationale and they should be considered only in selected cases.

Non-Invasive Ventilation. Although there is a sound evidence for the use of non-invasive ventilation (NIV) in acute exacerbations of chronic obstructive lung disease, its use in asthma is controversial. Objective evidence of benefit is very limited; a recent Cochrane review^[7] could only find one well-conducted prospective, randomized trial of just 30 patients that showed improvements in the respiratory rates in asthmatics with mild to moderate exacerbations when NIV was added to the standard medical care. Currently, the use of NIV in even mild to moderate exacerbations of asthma cannot be recommended outside the randomized controlled trials. NIV has no role in the management of life-threatening exacerbations of asthma.

Heliox. Heliox (oxygen in helium) reduces the density of the gas mix to improve turbulent gas flow. Use has been reported in less severe acute exacerbations of asthma where, in spontaneously breathing patients, it may reduce the work of breathing. This use is not, however, supported by an evidence base and its utility is further limited by a maximum oxygen fraction of 0.4 making it unsuitable for those with life-threatening asthma. Use of heliox with a mechanical ventilator is complex, requiring the recalibration of the pneumotachographs and the use of density independent spirometry of exhaled gas flows.

Leukotriene Antagonists. Currently available leukotriene antagonists (Montelukast, Zafirlukast) have no role in management of life-threatening asthma.

Monoclonal Anti-IgE Antibodies. Omalizumab is thought to be effective at reducing the number and possibly the severity of acute exacerbations of asthma in adults with moderate to severe allergic asthma that is inadequately controlled by inhaled steroids. It is a preventative measure and has no role in the management of acute life-threatening episodes.