Regional anesthesia – a critical assessment

REGIONAL ANESTHESIA – A CRITICAL ASSESSMENT I feel signally honored to have the privilege of giving the annual Rovenstine Lecture. The Honor is heightened both by pleasure and humility – my years with him were cherished. The opportunities which he provided for me are impossible to describe fully and to express sufficiently my gratitude to him. I have undertaken a critical discussion of a subject that was dear to his heart – a field that has always fascinated me as it did him – the field of therapeutic and diagnostic nerve blocks. It is one that I find perplexing now. I wish to share these controversial and puzzled views with you, from the perspective of old and recent developments in this field. Before doing so, I wish to pay a short tribute to a great man in words which, I hope, will also set the background for the remainder of this lecture in his honor and in his memory. E.A. Rovenstine, whose photograph I show you, (Fig. 1) was one of the most distinguished of anesthesiologists of his time. He may very well have had a greater influence on the development of this specialty than any other physician because of his versatility as a teacher, clinician, and clinical investigator. Born in Atwood, Indiana, in 1895 and educated at Wabash College and the University of Indiana, Rovenstine came to New York from Wisconsin in 1935 to start the first academic department of anesthesiology in that city. His medical interests were incredibly wide and his skills magnificent. He was far ahead of his time in recognizing the future importance of the physical as well as the biological sciences to anesthesiology. He predicted as early as 1947 that physics, electronics, and even automatic devices would one day have a great He had remarkable interest in the application of regional anesthetic procedures to surgical operations. He extended this interest thereafter to the study and therapy of other diseases, many of them painful: hence our discourse of pain control today. He brought the knowledge of the anesthesiologist in the control of pain to aid in the diagnosis and therapy of many different diseases. His favorite clinical problems for regional block were patients with trigeminal neuralgia, the painful shoulder, and the causalgic states. The pain of cancer interested him to a lesser degree, an irony of sorts in view of his eventual tragic battle with a prostatic cancer which finally took him from us in 1960. His marked curiosity and interest in painful states was a logical development in view of the opportunities that Rovenstine had and utilized to further this particular skill. He was, in fact, almost preoccupied with this aspect of anesthetic care. His interest in this field began when he met Gaston Labat, the distinguished French surgeon who had turned regional anesthetist. Labat at the time was performing much of the regional anesthesia in Bellevue Hospital and also consulted at the Presbyterian Hospital in New York. Rovenstine also became a close friend of another surgeon interested in regional anesthesia who remained a practicing surgeon, Dr. Hippolyte Wertheim. The welding of the superb anatomical knowledge of Wertheim and the amazing technical skill of Labat with the inquisitive scholarly and clinical knowledge of Rovenstine, resulted in a cohesive direct attack upon the problems of diagnosis, prognosis and therapy of diverse abnormalities which had in common only the transmission of impulses painful or Rovenstine’s interest in therapeutic nerve block carried him to the point where he intended to write, with Madame Labat’s approval, a second edition of Labat’s classic book on Regional Anesthesia. He never produced this work because he disliked the discipline of tedious application necessary in the compilation, digestion, and production of material for book-writing. He preferred to look forward to new things rather than write about the old – even though he wrote easily and with a grace that had ever so small a touch of the flowery. However, he did secure from Madame Labat a large collection of drawings and plates which were to be used for a subsequent edition of the book. Some of these magnificent drawings have, fortunately, not been lost, and were utilized by Vincent J. Collins in his text books on anesthesiology. Many new drawings and plates were also commissioned and drawn by a now well known artist, a friend of mine from World War II days, Caroll N. Jones, Jr.; some of these have also appeared in Collins’ works. Rovenstine’s interest in this subject carried him even further. He instituted courses in cadaver dissection in regional anesthesia which were available to the residents of the Bellevue Hospital Department and were also highly popular with anesthesiologists from other parts of the country. Among the students in these early courses were Doctors Dripps, Lamont, Collins and Gonzalez – to name only a few individuals who subsequently achieved prominence. Rovenstine taught much of the didactic part of this course and was a demonstrator of therapeutic nerve block on patients for the students. He was always at his best when he could demonstrate before and teach a group of Rovenstine’s attitude toward the control of pain In a paper in which I had the privilege of being co-author published in 1948, we described the obligation of the anesthesiologist and his opportunity to participate in the therapeutics of pain, in this way – “But events in the changing medical world have made it imperative that our functions be broadened and we accept the challenge of pain occurring outside the surgical amphitheater. Such a concept fully justifies an anesthesia clinic on the therapy of pain.” We wanted to help people because – “Pain whose unheeded and familiar speech is howling and keen, shrieks day after day.” – as Shelley General remarks as justification for considering a critical assessment of the place One of the underlying problems in the assessment of nerve block is that the literature is prolific in praising and recommending the value of nerve blocks in an uncritical way, and does not take fully into account some of the problems that have to be considered. This statement shows some of the problems encountered in my reading. Sphenopalatine block was good for all that ails you! We shall concern ourselves with a detailed consideration of a few of the problems and raise some of the questions that need be asked. It is important to state at this point that one of the tacit assumptions always made by writers in the field is that the simple interruption of a conducting pathway is destined by that very act to prevent noxious, harmful or painful impulses from reaching the central nervous system, and therefore to alleviate discomfort. This is not necessarily so as we shall see for a multitude of variables impinge on the therapeutic value of nerve block. Recent clinical experience at The Columbia – Presbyterian Medical Center Table 3 summarizes some of the recent experiences at the Presbyterian Hospital on this subject. It will be noted that of the total number of procedures, something over 1300 performed in the last 4 ½ years, that approximately 60 percent were done for therapeutic purposes and some 40% for diagnostic purposes. The diagnostic aspect of regional anesthesia is very often neglected: its role here is extraordinarily useful and critically important in selecting those patients in whom surgery or psychiatry may offer definitive help. In 1965, Jones of the Mayo Clinic suggested that neurosurgery may be the treatment for certain painful states, and that diagnostic nerve block may be useful in indicating in which of these states it may be applied: e.g., pain over the distribution of a peripheral nerve may be better controlled by neurectomy; pain over the distribution of a spinal nerve may be better controlled by rhizotomy. The latter preserves motor function and can destroy the sensory function of a nerve; it is therefore more selective than nerve block. Pain over an extensive area can be best controlled by chordotomy which may be attended by fewer complications than multiple injections in nerves. Perhaps just as important but almost never mentioned is that nerve block can sort out those patients that would be poorly managed by either surgery or destructive nerve block with phenol or For instance, one of the procedures that we have found valuable even in pain resulting from cancer is to do a “dummy” or placebo nerve block with saline, in order to evaluate the effect of psychological factors in the genesis of pain. The placebo block connotes a potent procedure to a patient, i.e., the insertion of needles and the implied promise of relief from suffering. The placebo effect can be great and it must be evaluated for at least two reasons. The decision to destroy a nerve requires that one be absolutely certain that the nerve must be destroyed in order to relieve the symptom, otherwise the patient has a great disservice rendered to him. The understanding of pain or the disturbed neurophysiological process implies that the removal of nerve impulses is critical to alteration of the syndrome. In our hands, the placebo effect of saline block has been important in something over 30% of all patient studies, regardless of the source of pain. The obvious conclusion from such experience is that a block with saline should be done in at least the doubtful cases. The incidence of pain relief after a block with a local anesthetic must clearly exceed 30% in order to be acceptable as a useful clinical procedure. Therefore, as a practical measure, I would recommend that a block with saline be instituted after a successful block with an aqueous solution of a local anesthetic, before making a definitive judgment as to the ultimate therapeutic procedure to be used if At The Presbyterian Hospital in the last 4 ½ years the largest number of patients were in-patients, and approximately little more than 1/3 were outpatients. It is also of interest that over this period when diagnostic and therapeutic nerve blocks were in relative disfavor and on the decline, there were nonetheless still nearly 300 blocks preformed on average, per year. These comprised 1.1% of all anesthetic procedures done by the Department of Anesthesiology and some 7% of all regional anesthetic procedures. Prior to 1962, more diagnostic and therapeutic blocks were performed for more diseases than is true at present. Some reasons for this decline will be discussed. The uncertainties and disquietudes about the role of regional anesthesia in clinical conditions, especially in painful states, may be the result of a variety of factors; one is lack of understanding of the mechanism of pain. For instance, the basic assumption that the destruction of a neuronal carrier of impulses to the central nervous system is the way to attack pain could be wrong or at the least only partially adequate for some disorders. The anesthesiologist must understand and do something about unraveling the mechanism of pain in order to evaluate his participation as a therapist. A definition of pain is extraordinarily difficult to phrase because it is basically a subjective sensation which can properly be experienced by the person who has it, and not all people experience pain. It has been stated that the pain experience is the sensation derived from noxious impulses traveling specific pathways, and that such phenomena may be followed by the familiar and predictable feeling states. This “specific” theory has been known as the physiological theory of pain. It certainly does not explain all the phenomena of pain. For instance, the impulse which causes a feeling of pain may certainly not be noxious. A light brush of the skin in a patient with causalgia can cause the most unholy of terrors. The pathways are certainly far from specific – a concept Also, the concept that there is a specific sensory unit consisting of specific free branched naked nerve endings in the periphery, especially the skin, which are connected to a single cell in the dorsal root ganglion, is clearly naïve in the light of recent studies. Another objection to the “specific” concept is that there are patients who are congenitally insensitive to pain and as far as one can tell have absolutely normally conductive neural pathways. There are the classic papers of Jewesbury and others, who describe this finding. In fact, one went so far as to state that pain was not an essential biological adjustment and cited three boys, brothers, with insensitive skins who plagued their mother by exhibitionistic self-torture. The spatial or psychological theory of pain. This concept contends that pain is an interpretive rather than a specific phenomenon. The proponents of this theory believed that neurophysiologically a change in the intensity of the stimulus may progress through sensations of touch, heat and pain, all carried over the same neural pathways. In certain diseases or abnormal states touch may be interpreted as pain. Examples of these conditions are causalgia, spinal anesthesia and nerve block anesthesia for operation. The past experience of the patient also enters into the interpretation of the phenomenon. Adding immeasurably to these concepts is the suggestion that an internuncial group of neurons can become hypersensitive because of repetitive bombardment at different rates of speed, through short and long fibers, and become hyperconductors, as it were, of normal stimuli. This was the so called “irritable focus” by which the persistent pain of causalgia and other states was propagated. This theory has also been shown to be Neither of these theories adequately explains all aspects of the mechanism of pain. A new theory of the mechanism has just been proposed; the so called gateway theory, by Wall and his associates. Insufficient time has elapsed to interpret the impact of the Wall theory on the comprehension of the pain process. I recommend that the studies of these investigators be watched with interest as they appear. Even if one assumes that there is sufficient knowledge about which nerves are to be blocked, diagnostically or therapeutically, the question arises as to how accurately one can place a needle near the nerve to be blocked, through the unbroken skin. It goes without saying that a precise knowledge of anatomy is extremely important so that the regional anesthesiologist can visualize the direction of the thrust of his needle. He should have a three dimensional sense as to where needles should go in relation to bony landmarks and soft tissues. There is no substitution for repeated cadaver dissection for However, even with this knowledge, there are certain points about the accuracy of needle placement that are useful. One should not be bound by tradition in the technical approaches to nerve block. For instance, paravertebral thoracic and lumbar somatic block are still performed by the method of Labat or the modifications of Rovenstine: these methods are not wholly satisfactory. A more accurate method for these blocks has been described by Shaw. The technique has, unfortunately, not gained popularity probably owing to lack of awareness of its description. This approach is shown in Fig. 2, not only as a good method in itself, but as illustration of the fact that technical proficiency in nerve block has not died with the old masters and that a renewed study of applied neuroanatomy will be rewarding to those interested in this field. The proper placement of the needle requires as much assistance as can be obtained. One of the ways in which this has been done was advocated by Greenblatt and Denson in 1962. (Table 3) This method involves the use of an electrical stimulator to locate the peripheral nerves. These authors found a relationship between the voltage required to stimulate and the distance from the nerve. If nerve destruction is contemplated, obviously the closer the needle is to the nerve the greater the likelihood of success. Our experience with electrical stimulation has been good in those procedures wherein precise location of nerves is difficult, e.g., obturator nerve block. It is not the complete answer to those blocks which must be done with destructive agents, although it Another method of precise location of the place of injection is by use of radiographic control. By and large the anesthesiologist will do well to associate himself with a skilled person in radiology, preferably one with an interest in neuroradiology. Figures 3 and 4 are from studies done in collaboration with Doctor Gordon Potts of the Department of Radiology at Columbia University. The first of these is a basilar view of the skull which has been retouched with barium to demonstrate the openings of the foramina ovale. This approach is most useful for the proper performance of gasserian ganglion block. A lateral view (not shown) is also necessary. The second figure is a lateral view employing radiographic control in the performance of block of mandibular branch of the Fifth Nerve. This needle at the foramen ovale is and perhaps should have been retouched for greater clarity. The patient was an intelligent, middle-aged female teacher of psychology who had a classical tic douloureux of the third division of the Fifth Nerve. The true nature of the pain was proven on two separate occasions with block with lidocaine (xylocaine) and subsequently with saline. This figure demonstrates the value of radiography in locating the exit of the nerve from the foramen ovale. THE PROBLEM OF ANESTHETIC AGENTS TO BE USED It is apparent that the anesthesiologist must have a clear concept of the materials to be used in order to achieve diagnosis and adequate results with regional anesthetic methods. If the goal is that of nerve destruction he must recognize the fact that the commonly used neurolytic agents, absolute alcohol and phenol, produce a relatively small area of destruction, approximately a few millimeters for one ml. of the substance used. He must also recognize that there will be some degree of neural irritation produced in a certain number of patients. The incidence of neuropathy with heightened pain patterns is variably reported, but in our experience affects nearly 10% of those patients treated locally with absolute alcohol. The neuropathy is believed to be due to partial In addition, the anesthesiologist must be aware (even if he does not use them) that such modalities as ultra sound, radioactive materials (e.g., radioactive Strontium-Yttrium in a dose range of 50 millicuries or so) can also used for nerve destruction via properly In those circumstances where he intends to use aqueous solution of anesthetics for therapeutic effect or diagnostic purposes, the anesthesiologist should understand something of the mechanism of action of these drugs in order to predict the result. Without such understanding the discovery of new drugs is subject to delay or doomed to To summarize the essentials -- it is now conceded that aqueous local anesthetics work by interference with uptake of sodium by the nerve. This mechanism has been clarified by recent studies on tetrodotoxin, a potent poison extracted from the tissues of the puffer fish. This substance blocks only uptake of sodium and is probably the most potent local anesthetic agent known since it produces a permanent state of non- conduction. Most of the conventional local anesthetics block sodium uptake by the nerve cells, and appear, in addition, to exert an influence on potassium flux. However, this mechanism is not uniformly agreed upon. The work of Ritchie at the Albert Einstein College of Medicine suggests that the basic form of the local anesthetic is necessary for penetration of the nerve sheath, but that the activity at the nerve membrane depends upon ionization. Ritchie’s observations have been confirmed with employment of the type of Ringer’s solution that he uses. However, if the Ringer’s solution is of the more conventional type, the classic view that the basic form of the local anesthetic is more active is supported regardless of whether one is dealing with a myelinated or Other physiological changes also influence nerve conduction. For example, carbon dioxide has a depressant effect upon nerve conduction. In order to evaluate the effects on nerves of aqueous solutions of anesthetics for diagnosis and therapy such considerations must be borne in mind. It is not sufficient to say that patients vary so much that patient variability will account for the changes. When one looks at the experimental data and thinks of synthesis of new local anesthetic agents which may be time controlled for various purposes, it appears as though the most exciting advance in recent years in the chemistry of local anesthetics may lie in unraveling the complicated structure of tetrodotoxin. It is a fascinating material in many ways including the fact that it has a very low lipid solubility. Classically, it has always been stated that the effective local anesthetics must have a high lipid solubility. Chemists are attempting to synthesize tetrodotoxin and to modify it chemically in order to produce local anesthetics with the desired spectrum of effects. In addition to matters of technical skill and chemical solutions, the total management of a patient in need of therapeutic regional anesthesia is of considerable importance. The physician must choose his patients, must be aware of the natural history of the diseases that he is concerned with, and must recognize the role that he plays as a physician in the overall management of a patient who requires regional anesthetic procedures. In light of these comments it would serve us well to consider some specific problems that have been dealt with over the years with regional anesthetic methods Much has been written on this subject and it is well to examine some of the results obtained so that the anesthesiologist will be provided with information with which to compare his own experience. The female gastrourinary tract, the breast, the pelvis and the lower gastrointestinal tract account for over 50% of the pain resulting from malignant disease. (Table 4) Most patients fall into the middle-age group. The large majority of patients have pain somewhat less than six months when they present themselves for treatment. In the normal course of events, palliative surgery, radiation and narcotics are the most commonly used procedures in the therapy of cancer pain. (Table 5) When cancer pain is systematically attacked by a group of physicians interested in the problem, nerve block, chordotomy and narcotics become the mainstays of treatment. This is not surprising in view of the fact that the large majority of patients have pain in those nerve tracts amenable to destruction either by regional anesthetics or by operation, i.e., the female gastrourinary tract, the breast, the pelvis. This is also a commentary on how much more important nerve block could become in planned therapy. Examples from the literature on this subject will be cited. Nerve block therapy for cancer patients, according to Bonica, yields approximately a 60 percent complete relief of pain and nearly 15% failure, with intermediary effects in the others. These results should be evaluated in accordance with the now well established placebo effect, that is a 30 % “cure” rate for any therapeutic The use of subarachnoid alcohol block has waxed and waned over the years. The results of one study are shown in table 7 in which approximately 50% of patients were completely relieved of pain due to cancer and another 33% had partial relief. These data must also be interpreted cautiously in view of the placebo effect and the fact that this method has not really stood the test of time. Despite reported successes, our experience at the Presbyterian Hospital with splanchnic nerve block or subarachnoid alcohol block for visceral pain, especially that due to extension from hollow organs or the pancreas has been disappointing. We have done very much better for the relief of pain in those patients who have extension to skeletal areas that are amenable to segmental paravertebral block according to the method of Shaw, and where life expectancy would We have also had success in treating cancer pain in those areas which are within the clearly defined limits of a peripheral nerve, e.g., a cranial nerve especially a branch of the fifth nerve. Some types of head and neck cancer pain are well treated in this way. A question still remains as to why various methods of treatment appear to help approximately two thirds of patients with cancer pain, limited to a period of months. No biological explanation is yet available and studies are sorely needed. A problem presents itself in Tic Douloureux which is of great interest and illustrates one of the reasons why anesthesiologists must be alert to the development of new concepts in the control of pain. The use of nerve block for the treatment of trigeminal neuralgia is time-honored and very impressive in most reports. In fact, it is one of the favorite diseases for which nerve block was used by Rovenstine and his associates. As is commonly the case in all painful states, it is instructive to look at the natural history of the disease before we attempt to evaluate the results of treatment. Rushton at the Mayo Clinic, as early as 1953, analyzed the natural history of the disease, and showed that in trigeminal neuralgia, approximately 50 percent of patients had a spontaneous remission for six months or more. (Table 8) Approximately 25 percent of patients had a spontaneous remission for more than one year. This obviously means that one is unable to judge the efficacy of nerve block or any other procedure without taking into account the natural history. I would think that pain relief in 60% of patients by nerve block might not be as impressive as it sounds, unless the relief were either permanent or were of the magnitude of two years or more. Obviously clinical judgment must temper this opinion and one should not be too harsh in making the judgment; but it is well to keep in mind what the story can be with and without treatment. The problem is even complicated by newly developed specific drugs for the therapy of tic douloureux; - one of these drugs studied by Amols at our institution is Tegretol, a drug which is both anticonvulsive and a psychic energizer. Using Tegretol Amols attained sustained relief of pain for a period of two years and a remission incidence after Tegretol was discontinued, of some 20%, in trigeminal neuralgia. (Table The drug is not harmless in that is produces complications referable to the blood- forming elements and to the central nervous system in about 10% of patients. However, treatment is so useful with this drug that it has completely changed the picture of nerve block and the need for intracranial operation at our Neurological Institute. It can be seen from the next chart that in the third year of the drug study there were no intracranial 5th nerve operations and very few nerve blocks except in Tegretol failures compared to an average of 28.1 intracranial operations annually prior to the use of this drug. Nerve block therapy of should pain, one of the most impressive and popular that Rovenstine used, has receded to a position of historical interest because of the combined effects of anti-inflammatory agents, the direct injection of such substances as cortisone into inflamed areas in the shoulder and the greatly increased sophistication of rehabilitation procedures for these patients. It can be truly said that the nerve block treatment for shoulder pain is obsolete except in rare instances. Nerve block was very widely used to produce vasodilatation. It was most commonly performed in the approach to diseases of the extremities characterized by vasospasm. The most common methods used were stellate and thoracic sympathetic block for the upper extremities and epidural block and lumbar sympathetic for the lower extremities. These methods, too, have seen less frequent use except for problems in the lower extremities where epidural block has retained a place of usefulness. Here it provides surgical anesthesia as well as vasodilatation for operations that may prove to be necessary. An important reason for the change in approach to these diseases appears to be the remarkable progress of vascular surgery in which the combination of parenteral vasodilating agents can be used with reconstruction of peripheral vessels of varying size, including very small vessels. Even nerve injury, a previously important cause of causalgia, is susceptible to better repair with newer techniques. An example of another type of block that has fallen into relative disuse is stellate ganglion block for the treatment of cerebral vascular insufficiency and stroke. It is now well established that the major control of the cerebral circulation lies in the PCO2 of arterial blood in the cerebral vessels and not via neural vasomotor tone. Therefore, nerve block is not rational. Although never widely accepted, the block is not used now for the treatment of asthma in view of the greatly increased efficiency of drug treatment of this disease coupled with the rehabilitative approaches to proper respiration, and the use of It appears therefore that there has been a significant change in the direction of diminution of the importance of diagnostic and therapeutic nerve blocks as a traditional form of therapy. This is largely the result of the changing and increasingly successful pattern of therapeutics with drugs and surgical procedures. The listener has the right to expect a more definitive answer from a speaker who has told you essentially that there are not only many problems concerning diagnostic and therapeutic nerve block, but that the method has lost usefulness. How do diagnostic and therapeutic block fit into The answers based upon analysis fall into two main categories. One obvious thought is that the regional anesthesiologist, who chooses to use these methods must learn more about percisional anatomy, the potential, the nature of, and the development of both destructive agents and temporarily active anesthetics if his patients are to benefit. He must also become familiar with other methods of destroying nerves. He must take an interest in the precise localization of his needles. He must take a strong interest in understanding the mechanisms of pain so that he does not function as a technician whose results turn out, by and large, to be unsatisfactory and who will cease to have patients referred to him for treatment because of his failures. He must be in the position, if interested in the problems, to take part both in the total care of the patients and to contribute to a better understanding of the problems of pain. If these essentials are achieved, then a list of useful procedures, as seen by this observer, can be developed, one that he owes to this audience in view of his critical and unfavorable comments 1. To establish with certainty whether pain is organic or functional in nature. 2. To decide whether surgical destruction or destructive nerve block of a given conducting pathway is advisable or necessary. 3. To aid in the differential diagnosis of the source of pain, e.g., pain can reverberate from one area to another subserved by a branch of a major nerve. It is possible to have toothache in the lower jaw originating from a lesion in the upper jaw. These can be differentiated by appropriate diagnostic blocks. 4. The use of nerve block procedures as a research method in unraveling the B. Therapeutic nerve block – present values. 1. Therapeutic block of a temporary nature is valuable in the management of certain self-limited processes which would ordinarily require substantial doses of narcotics, or the interference with other physiological functions. The use of paravertebral block for the management of patients with fractured ribs is a 2. Control of postoperative pain. This is a method that is insufficiently used because of problems in the extravagant use of personnel. However, where necessary and where possible, the management of postoperative pain without narcotics and without restrictive dressings is a most valuable aspect of diagnostic and therapeutic block. It should be used much more often than it 3. The epidural route is useful when the combined vasodilatation and surgical 4. The management of pain in labor, prior to obstetrical delivery. 5. Another use of epidural block is found in patients with peripheral vascular disease who are undergoing definitive operations upon blood vessels. 6. In the management of pain resulting from cancer, the method has merit if the cancer is confined to the distribution of a readily accessible peripheral nerve 7. In the study of baffling clinical problems where nerve interruption will be helpful in correcting the abnormal physiology of congenital urinary tract 9. In patients where the newer drugs have failed to provide relief. 1. An analysis from a historical, physiological, pharmacological and clinical point of view of those elements that are concerned with critical assessment of the role of regional anesthesia in diagnostic procedures and therapeutics has 2. Some of the traditional uses of this method are outmoded and have become 3. Suggestions as to those areas of clinical practice where diagnostic and therapeutic block is useful have been made.



International Journal of Antimicrobial Agents 21 (2003) 267 Á/273b-lactamase production in Provotella and in vitro susceptibilities toL. Dubreuil a,, J. Behra-Miellet a, C. Vouillot a, S. Bland b, A. Sedallian b, F. Mory ca Faculte´ de Pharmacie, 3, rue du Professeur Laguesse, BP83, Lille Cedex 59006, FranceReceived 21 May 2002; accepted 1 July 2002This study looked for b-lactamase producti

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