5. If there be a sufficiency of the original material, Merck’s process

for detecting porphyroxin may be tried [see p. 534]. But I doubt whether this process is sufficiently delicate for medico-legal purposes. I wish I could add my testimony to the opinion, expressed on a remarkable occasion by Professor Chaussier, in favour of the delicacy of the tests for morphia and its compounds, that they might be detected “jusqu’à une molécule.”[1685] In one sense this statement may be correct. Morphia, separated from the complex mixture of principles with which it is combined in opium, may be detected in extremely small quantities. Accordingly, M. Lassaigne has supplied, for the discovery of acetate of morphia in mixed fluids, an excellent process, whence the chief part of the three first paragraphs of the preceding method for opium are borrowed; and from the facts stated by him in his paper,[1686] as well as from the experimental testimony of Professor Orfila,[1687] it appears that Lassaigne’s process will furnish strong indications, if not absolute proof of the presence of that salt, in the proportion of two grains to eight ounces of the most complex mixtures. Hence the search for acetate of morphia in a suspected case is by no means hopeless. But the detection of acetate of morphia is an object of small moment, compared with the detection of morphia in its natural state of combination in opium. Now my own observations lead me to entertain serious doubts, whether the best method of operating hitherto known could be successfully applied to the detection of the equivalent opium in complex mixtures. By the process I have recommended it is easy to procure, from an infusion of ten grains of opium in four ounces of water, satisfactory proof of the presence of morphia by the action of ammonia, perchloride of iron and nitric acid, and equally distinct proof of the presence of meconic acid by perchloride of iron, as well as sulphate of copper. But on proceeding to apply the process to organic mixtures, I have found that when the soluble part of ten grains of opium was mixed with four ounces of porter or milk, I could develope no property of morphia but its bitterness, and no indication of meconic acid but the action of perchloride of iron. MM. Larocque and Thibierge, it is right to add, have in similar circumstances found the process somewhat more delicate.[1688] It is of great consequence, however, to remark, that in cases of poisoning with opium, the medical jurist will seldom have the good fortune to operate even upon so large a proportion of the poison as in my experiments; because the greater part of it disappears from the stomach before death. This will not happen always, as may be seen from various cases mentioned afterwards in the section on the morbid appearances caused by opium. But, according to my own observations, the poison will often disappear in a short time, so far as to render an analysis abortive. Thus in the case of a young woman who died five hours after taking not less than two ounces of laudanum, I could apply to the fluid, procured from the contents of the stomach, by paragraphs 1, 2, and 3 of my process, only the test of its taste, which had the bitterness of morphia. In the case of another young woman, whose stomach was emptied by the stomach-pump four hours after she took two ounces of laudanum, I could obtain from the evacuated fluid, when properly prepared, only the indications of the presence of morphia supplied by its bitterness and the imperfect action of nitric acid,—and the indication of the presence of meconic acid supplied by the imperfect action of perchloride of iron. In a third case, where the stomach was evacuated two hours after seven drachms of laudanum had been swallowed, even the first portions of fluid withdrawn had not any opiate odour, and did not yield any indication of the presence even of meconic acid. Now, on the one hand, the quantity taken in these instances is rarely exceeded in cases of poisoning with laudanum; and, on the other hand, the interval during which it remained in the stomach subject to vital operations is considerably less than the average in medico-legal, and above all in fatal cases. It may be laid down, therefore, as a general rule, that in poisoning with opium the medical jurist, by the best methods of analysis yet known, will often fail in procuring satisfactory evidence, and sometimes fail to obtain any evidence at all, of the existence of the poison in the contents of the stomach. In a case published by Dr. Bright from the experience of Mr. Walne of London, it is stated that the matter removed from the stomach only half an hour after an ounce and a half of laudanum had been taken, while the stomach was empty, did not smell of opium.[1689] This case is quoted to put the reader on his guard. But at the same time it does appear extremely improbable that the whole opium had disappeared from the stomach in so short a time, and much more likely that it might have been found by analysis in the matter first withdrawn. I have taken some pains to establish the proposition laid down above, because in a matter of such importance it is always essential, that the medical inspector know the real extent of his resources; and it has appeared to me that, greatly as the hand of the chemist has been strengthened by late discoveries in vegetable analysis, his power has been overrated both by his scientific brethren, and by the medical profession generally. I am happy to find, since the first publication of these remarks, that they coincide with the experience and opinion of so eminent an authority as Professor Buchner; who has observed that a chemical analysis must often fail to detect opium where there could be no doubt of its having been administered in large quantity.[1690] It is of moment to add, that in two of the instances mentioned above the odour of laudanum was perceived in the subject of analysis,—faintly, however, and only for a few hours after it was removed from the stomach. Although the peculiar odour of opium is a delicate criterion of its presence, it does not follow that it should be preferred to an elaborate chemical analysis. For it is a test of extreme uncertainty. There is in the contents of the stomach such a complication of odours, that with a rather delicate sense of smell, I have sometimes been unable to satisfy myself of the presence of the opiate odour where others were sure it existed. At the same time the medical jurist should not neglect it as a subsidiary test. It is always strongest and most characteristic, first, when the stomach is just opened, or the contents just withdrawn, and again, when the fluid, in the course of preparation, as directed in paragraph 1 (p. 535), is just reaching the point of ebullition. The latter odour is somewhat different from the former, yet quite peculiar, and such as every chemist must have remarked on boiling an infusion of opium. It is further to be observed, that although the odour of opium is a very delicate test of its presence even in complex organic mixtures, chemical analysis may be successful, where this character fails. Dr. Morehead of the Bombay service, in applying my process to the fluid withdrawn by the stomach-pump, detected morphia both by nitric acid and perchloride of iron, although he could not detect any odour of opium in the fluid.[1691] So much for the delicacy of the process. As to its precision,—from what I have myself witnessed, as well as from the experience of Dr. Ure, it will often happen in actual practice, that the only indication of opium to be procured by the process consists in the deep red colour struck by perchloride of iron with the meconic acid. Now, will this alone constitute sufficient proof of the presence of opium? On the whole, I am inclined to reply in the affirmative. Sulpho-cyanic acid, it is true, has the same effect, and this acid has been proved by Professors Gmelin and Tiedemann to exist in the human saliva,[1692]—a fact which was called in question by Dr. Ure in his evidence on the trial of the Stuarts, but which at the time I had verified, and which Dr. Ure has since been compelled by experiments of his own to admit.[1693] But it must be very seldom possible to procure a distinct blood-red coloration from the saliva, after it has been mixed with the complex contents of the stomach, and subjected to the process of analysis detailed above;[1694] and the check proposed by Dr. Percy (p. 532) will distinguish it. SECTION II.—_Of the Action of Opium, and the Symptoms it excites in Man._ The symptoms and mode of action of opium have been long made the subject of dispute, both among physicians and toxicologists; and in some particulars our knowledge is still vague and insufficient. Under the head of general poisoning, some experiments were related, from which it might be inferred that opium has the power of stupefying or suspending the irritability of the parts to which it is immediately applied. The most unequivocal of these facts, which occurred to Dr. Wilson Philip, was instant paralysis of the intestines of a dog, when an infusion of opium was applied to their mucous coat;[1695] another hardly less decisive was palsy of the hind-legs of a frog, observed by Dr. Monro Secundus, when opium was injected between the skin and the muscles;[1696] and a third, which has been remarked by several experimentalists, is immediate cessation of the contractions of the frog’s heart when opium is applied to its inner surface.[1697] The poison has also powerful constitutional or remote effects, which are chiefly produced on the brain. Much discussion has arisen on the question, whether these constitutional effects are owing to the conveyance of the local torpor along the nerves to the brain, or to the poison being absorbed, and so acting on the brain through the blood. The question is not yet settled. It appears pretty certain, however, that the poison cannot act constitutionally without entering the blood-vessels; although it is not so clear, that after it has entered them, it acts by being carried with the blood to the brain. The newest doctrine supposes that it enters the blood-vessels, and produces on their inner coat an impression which is conveyed along the nerves. According to the experiments of Professor Orfila, it is more energetic when applied to the surface of a wound than when introduced into the stomach, and most energetic of all when injected into a vein.[1698] The inference generally drawn from these and other analogous experiments[1699] is, that the blood transmits the poison in substance to the brain. They certainly, however, do not prove more than that the poison must enter the blood before it acts. The old doctrine, that the blood-vessels have no concern with its action, and that it acts only by conveyance along the nerves of a peculiar local torpor arising from its direct application to their sentient extremities, has been long abandoned by most physiologists as untenable. But some have adopted a late modification of this doctrine, by supposing that opium may act both by being carried with the blood to the brain, and by the transmission of local torpor along the nerves. They believe, in fact, that opium possesses a double mode of action,—through sympathy as well as through absorption. It would be fruitless to inquire into the grounds that exist for adopting or rejecting this doctrine, because sufficient facts are still wanting to decide the controversy. So far as they go, however, they appear adverse to the supposition of a conveyance of impressions along the nerves, without the previous entrance of the poison within the blood-vessels. The difficulties, in the way of the theory of the sympathetic action of opium, would be removed by the doctrine of Messrs. Morgan and Addison. According to their views, the experiments, which appear at first sight to prove that this substance operates by being carried with the blood to the part on which it acts, are easily explained by considering that the opium makes a peculiar impression on the inside of the vessels, which impression subsequently passes along the nerves to the brain.[1700] But, as stated in the introductory chapter on the physiology of poisoning, this theory requires support. The effects of opium, through whatever channel it may produce them, are exerted chiefly on the brain and nervous system. This appears from the experiments of a crowd of physiologists, as well as from the symptoms observed a thousand times in man. In animals the symptoms are different from those remarked in man. Some experimentalists have indeed witnessed in the higher orders of animals, as in the human subject, pure lethargy and coma. But the latest researches, among the rest those of M. Orfila, show that much more generally it causes in animals hurried pulse, giddiness, palsy of the hind-legs, convulsions of various degrees of intensity, from simple tremors to violent tetanus, and a peculiar slumber, in the midst of which a slight excitement rouses the animal and renews the convulsions. These symptoms are produced in whatever way the poison enters the body, whether by the stomach, or by a wound, or by direct injection into a vein, or by the rectum. In man, convulsions are sometimes excited; but much more commonly simple sopor and coma. According to the inquiries of M. Charret, which were extended to every class of the lower animals, opium produces three leading effects. It acts on the brain, causing congestion, and consequently sopor; on the general nervous centre as an irritant, exciting convulsions; and on the muscles as a direct sedative. It is poisonous to all animals,—man, carnivorous quadrupeds, the _rodentia_, birds, reptiles, amphibious animals, fishes, insects, and the _mollusca_. But of its three leading effects some are not produced in certain classes or orders of animals. In the _mammalia_, with the exception of man, there is no cerebral congestion induced, and death takes place amidst convulsions. In birds there is some cerebral congestion towards the close; but still the two other phenomena are the most prominent.[1701] It has been rendered probable, by what is stated above, that opium enters the blood. The question, therefore, naturally arises, whether its presence there can be proved by chemical analysis? But considering the imperfection of the processes for detecting it when mixed with organic substances, no disappointment ought to be felt if this proof should fail in regard to so complex a fluid as the blood. The only person who has represented himself successful in the search is M. Barruel of Paris. He examined the urine and blood of a man under the influence of a poisonous dose of laudanum, amounting to an ounce and a half; and procured indications of morphia in both. When three ounces of urine were boiled with magnesia, and the insoluble matter was collected, washed, dried, and boiled, in alcohol, the residue of the alcoholic solution formed a white stain, which became deep orange-red on the addition of nitric acid. The blood was subjected to a more complex operation. One pound and ten ounces of it were bruised in a mortar, diluted with two pounds of water, strongly acidulated with sulphuric acid, boiled, filtered, and washed. The filtered fluid was saturated with chalk, and the excess of carbonic acid driven off by heat. The fluid was then filtered again, and after being washed with water, was acted on by diluted acetic acid. The acetic solution left on evaporation a residue which was repeatedly acted on by alcohol; and the residue of the alcoholic solutions was treated with pure alcohol and carbonate of lime. The new solution when filtered and evaporated left several small white stains, which became orange-red with nitric acid.[1702] These results have been since contradicted by M. Dublanc. He in vain sought for morphia in the blood and urine of people who were taking acetate medicinally, or of animals that were killed by it.[1703] Barruel’s results are also at variance with some pointed experiments of M. Lassaigne, who could not detect any acetate of morphia even in blood drawn from a dog twelve hours after thirty-six grains were injected into the crural vein;[1704] nor any in the liver or venous blood of a dog poisoned with eight ounces of Sydenham’s laudanum.[1705] In investigating the effects of opium and its principles on man, the natural order of procedure is to consider in the first place those of opium itself in its various forms. The effect of a small dose seems to be generally in the first instance stimulating: the action of the heart and arteries is increased, and a slight sense of fulness is caused in the head. This stimulus differs much in different individuals. In most persons it is quite insignificant. In its highest degree it is well exemplified by Dr. Leigh in his Experimental Inquiry, as they occurred to a friend of his who repeatedly made the experiment. If in the evening when he felt sleepy, he took thirty drops of laudanum, he was enlivened so that he could resume his studies; and if, when the usual drowsiness approached, which it did in two hours, he took a hundred drops more, he soon became so much exhilarated, that he was compelled to laugh and sing and dance. The pulse meanwhile was full and strong, and the temporal arteries throbbed forcibly. In no long time the customary torpor ensued. The stimulant effect of opium given during a state of exhaustion is also well illustrated by Dr. Burnes in his account of Cutch. “On one occasion,” says he, “I had made a very fatiguing night march with a Cutchee horseman. In the morning, after having travelled above thirty miles, I was obliged to assent to his proposal of haulting for a few minutes, which he employed in sharing a quantity of about two drachms of opium between himself and his jaded horse. The effect of the dose was soon evident on both, for the horse finished a journey of forty miles with great apparent facility, and the rider absolutely became more active and intelligent.”[1706] By repeating small doses frequently, the stimulus may be kept up for a considerable time in some people. In this way are produced the remarkable effects said to be experienced by opium-eaters in the east. These effects seem to be in the first instance stimulant, the imagination being rendered brilliant, the passions exalted, and the muscular force increased; and this state endures for a considerable time before the usual stage of collapse supervenes. A very poetical, but I believe also a faithful, picture of the phenomena now alluded to is given in the Confessions of an English Opium-eater,—a work well known to be founded on the personal experience of the writer. It is singular that our profession should have observed these phenomena so little, as to be accused by him of having wholly misrepresented the action of the most common drug in medical practice. In reply to this charge the physician may simply observe, that he seldom administers opium in the way practised by the opium-eater; that when given in the usual therapeutic mode it rarely causes material excitement; that some professional people prefer giving it in frequent small doses, with the view of procuring its sedative effect, and undoubtedly do succeed in attaining their object; that in both of these medicinal ways of administering it, excitement is occasionally produced to a great degree and of a disagreeable kind; that the latter phenomena have been clearly traced to idiosyncrasy; and therefore that the effects on opium-eaters are probably owing either to the same cause, or to the modifying power of habit. This much at all events is certain,—that in persons unaccustomed to opium it seldom produces material excitement in a single small dose, and does not always cause continuous excitement when taken after the manner of the opium-eater. The effect of a full medicinal dose of two or three grains of solid opium, or forty or sixty grains of the tincture, is to produce in general a transient excitement and fulness of the pulse, but in a short time afterwards torpor and sleep, commonly succeeded in six, eight, or ten hours by headache, nausea, and dry tongue. The symptoms of poisoning with opium, administered at once in a dangerous dose, begin with giddiness and stupor, generally without any previous stimulus. The stupor rapidly increasing, the person soon becomes motionless and insensible to external impressions; he breathes slowly; generally lies still, with the eyes shut and the pupils contracted; and the whole expression of the countenance is that of deep and perfect repose. As the poisoning advances, the features become ghastly, the pulse feeble and imperceptible, the muscles excessively relaxed, and, unless assistance speedily arrive, death ensues. If recovery take place, the sopor is succeeded by prolonged sleep, which commonly ends in twenty-four or thirty-six hours, and is followed by nausea, vomiting, giddiness, and loathing of food. The period which elapses between the taking of the poison and the commencement of the symptoms is various. A large quantity, taken in the form of tincture, on an empty stomach, may begin to act in a few minutes; but for obvious reasons it is not easy to learn the precise fact as to this particular. Dr. Meyer, late medical inspector at Berlin, has related a case of poisoning with six ounces of the saffron tincture of opium, where the person was found in a hopeless state of coma in half an hour,[1707] and M. Ollivier has described another instance of a man who was found completely soporose at the same distance of time after taking an ounce and a half of laudanum.[1708] In these cases, the symptoms must have begun in ten or fifteen minutes at farthest. In a case noticed by M. Desruelles the sopor was fairly formed in fifteen minutes after two drachms of solid opium were taken.[1709] For the most part, however, opium, taken in the solid form, does not begin to act for half an hour or even almost a whole hour,—that period being required to allow its poisonous principles to be separated and absorbed by the bibulous vessels. It is singular that an interval of an hour was remarked in a case where the largest quantity was taken which has yet been recorded. The patient swallowed eight ounces of crude opium; but in an hour her physician found her able to tell connectedly all she had done; and she recovered.[1710] In some rare cases the sopor is put off for a longer period: thus, in a case mentioned in Corvisart’s Journal, there seems to have been no material stupor till considerably more than an hour after the person took two ounces and a half of the tincture with a drachm of the extract.[1711] The result of almost universal observation, however, is, that in pure poisoning with opium the commencement of the symptoms is not put off much beyond an hour. Such being the fact, it is extremely difficult to account for the following extraordinary case, which was communicated to me by Dr. Heude, of the East India Company’s service. A man swallowed an ounce and a half of laudanum, and in an hour half as much more, and then lay down in bed. Some excitement followed, and also numbness of the arms and legs. But he continued so sensible and lively seven hours after the first dose was taken, that a medical gentleman, who saw him at that time and got from him a confession of what he had done, very naturally did not believe his story. It was not till at least the eighteenth hour that stupor set in; but two hours later, when Dr. Heude first saw him, he laboured under all the characteristic symptoms of poisoning with opium in an aggravated degree. The stomach-pump brought away a fluid quite free of the odour of opium. In seven hours more, under assiduous treatment, after having been in an almost hopeless state of insensibility, he had recovered so far as to be safely left in charge of a friend; and eventually he got quite well. No particular cause could be discovered for the long apparent suspension of the usual effects of opium. Although the symptoms are very rarely postponed beyond an hour in pure poisoning with this substance, there is some reason for thinking that the interval may be much longer, if at the time of taking the opium the person be excited by intoxication from previously drinking spirits. Mr. Shearmen has related a striking case of an habitual drunkard, who took two ounces of laudanum while intoxicated to excitement with beer and spirits, and had no material stupor for five hours, during which period vomiting could not be induced. Five hours afterwards, he was found insensible, and he eventually died under symptoms of poisoning with opium.[1712] The most remarkable symptom in the generality of cases of poisoning with opium is the peculiar sopor. This state differs from coma, in as much as the patient continues long capable of being roused. It may be difficult to rouse him; but unless death is at hand, this may be commonly accomplished by brisk agitation, tickling the nostrils, loud speaking, or the injection of water into the ear. The state of restored consciousness is always imperfect, and is speedily followed again by lethargy when the exciting power is withheld.—It has been already remarked, that the possibility of thus interrupting the lethargy caused by opium is in general a good criterion for distinguishing the effects of this poison from apoplexy and epilepsy. It was observed, in describing the mode of action of opium, that convulsions, although very frequently produced by it in animals, are rarely caused in man. It is not easy to account for this difference. Orfila has endeavoured to explain it, by supposing that convulsions are produced only by very large doses; but there are many facts incompatible with that supposition. While convulsions are certainly not common in the human subject, yet when they do occur they are sometimes violent. Tralles mentions that he had himself several times seen convulsions excited in children by moderate doses.[1713] The Journal Universel contains the case of a soldier who took two drachms of solid opium, and died in six hours and a half, after being affected with locked-jaw and dreadful spasms.[1714] A case is related in the Medical and Physical Journal of a young man, who, three hours after swallowing an ounce of laudanum, was found insensible, with the mouth distorted, the jaws fixed, and the hands clenched; and who, soon after the insensibility was lessened by proper remedies, was seized with spasms of the back, neck, and extremities, so violent as to resemble opisthotonos.[1715] Another good case of the kind is related by Mr. M’Kechnie, where the voluntary muscles were violently convulsed in frequent paroxysms, and affected in the intervals with subsultus, for three hours before the sopor came on.[1716] Two instances of convulsions alternating with sopor are shortly related by Dr. Bright.[1717] The convulsions sometimes assume the form of permanent spasm, which may affect the whole muscles of the body, as in a case related in Corvisart’s Journal.[1718]—Another rare symptom of poisoning with opium is delirium. It appears to occur occasionally along with convulsions, as happened in Mr. M’Kechnie’s case, and in one related by M. Ollivier.[1719] The state of the pulse varies considerably. In an interesting case described by Dr. Marcet it is mentioned that the pulse was 90, feeble and irregular; and such appears to be its most common condition when the dose has been so large as seriously to endanger life.[1720] Frequently, however, it is much slower; and then it is rather full than feeble, just as in apoplexy. In cases where convulsions occur, it is for the most part hurried, and does not become slow till the coma becomes pure. In Mr. M’Kechnie’s case the pulse was at first 126; but when the convulsions ceased, and pure sopor supervened, it fell to 55. It always becomes towards the close very feeble, and at length imperceptible. The respiration is almost always slow. In Dr. Marcet’s case, as in some others, it was stertorous; but this is not common. On the contrary, it is more frequently soft and gentle, as it has been in all the cases I have witnessed; and sometimes it can hardly be perceived at all, even in persons who eventually recover, as in an instance of recovery recorded by Dr. Kinnis.[1721] The pupils are always at least sluggish in their contractions, often quite insensible;—sometimes, it is said, dilated:[1722] but much more commonly contracted, and occasionally to an extreme degree. In the case last noticed, they were no bigger than a pin’s head. The pupils have been so invariably found contracted in all recent cases of poisoning with opium, that some doubt arises whether they are ever otherwise, and whether the earlier accounts, which represent them to have been dilated, may not be incorrect, and the result of hasty observation. The expression of the countenance is for the most part remarkably placid, like that of a person in sound natural sleep. Occasionally there is an expression of anxiety mingled with the stupor. The face is commonly pale. Sometimes, however, it is flushed;[1723] and in rare cases the expression is furious.[1724] In moderately large doses opium generally suspends the excretion of urine and fæces; but it promotes perspiration. In dangerous cases the lethargy is sometimes accompanied with copious sweating. In a fatal case, which I examined judicially, the sheets were completely soaked to a considerable distance around the body. A remarkable circumstance, which has been noticed by a late author, is the sudden death of leeches applied to the body. The patient was a child who had been poisoned by too strong an injection of poppy-heads.[1725] In some instances the symptoms proper to poisoning with opium become complicated with those which belong rather to organic affections of the brain, in consequence of such affections being suddenly developed through means of the cerebral congestion occasioned by the poison. Thus, in a case related in Corvisart’s Journal, there were convulsions and somnolency on the third day, and palsy of one arm for four days; and for nearly two months afterwards the patient complained of occasional attacks of weakness and numbness, sometimes of one extremity, sometimes of another.[1726] Here the brain must have sustained some more permanent injury than usual.—A more remarkable illustration once occurred to Dr. Elliotson. A young man, seven hours after swallowing two ounces of laudanum, presented the usual effects of opium, such as contracted pupils, redness of the features, a frequent feeble pulse, coldness of the integuments, and stupor, from which he could be roused without particular difficulty. The stomach-pump brought away a fluid which had not any odour of opium; powerful stimulants were given, such as ether, ammonia and brandy; and he was kept constantly walking between two men. In an hour and a half, when sensibility had been materially restored, his head suddenly dropped down upon his breast, and he fell down dead. The sinuses and veins of the brain were turgid, and a moderately thick layer of blood was effused over the arachnoid membrane.[1727]—Under the same head must be arranged the following extraordinary case related by Pyl. That author admits it as one of simple poisoning, with a complete remission of the symptoms for several days. But the possibility of such a remission must be received with great hesitation. It is well known that most of the symptoms may be dispelled by vigorous treatment, and the patient nevertheless relapse immediately if left to himself, and even die. This is acknowledged on all hands. Pyl, however, admits the possibility of a much more complete and longer interval. His case is shortly as follows. A man who had taken a large quantity of opium, and became very dangerously ill, was made to vomit in twelve hours, and regained his senses completely. The bowels continued obstinately costive; but he had for some days no other symptom referrible to the poison; when at length the whole body became gradually palsied and stiff, and he died on the tenth day. No importance can be attached to a solitary case differing so widely from every other. The only way in which opium could cause death in such a manner, must be by calling forth some disposition to natural disease. Pyl’s case was probably one of supervening _ramollissement_, or inflammation of the substance of the brain.[1728] Notwithstanding the purely narcotic or nervous symptoms, which opium produces in a vast proportion of instances, there is no doubt that it also excites in a few rare cases those of irritation. Thus, although it generally constipates the bowels, it has been known to induce diarrhœa or colic in particular constitutions. In the first volume of the Medical Communications, it is observed by Michaëlis that both diarrhœa and diuresis may be produced by it. The soldier, whose case was quoted as having been accompanied with convulsions, had acute pain in the stomach for some time after swallowing the poison; and in the case just quoted from Corvisart’s Journal, the accession of somnolency was attended with excruciating pain of two days’ duration. Another and more singular anomaly is the spontaneous occurrence of vomiting. Sometimes a little vomiting immediately succeeds the taking of the poison. This may not interrupt, however, the progress of the symptoms;[1729] but more commonly it is the means of saving the person’s life, as in a striking case described by Petit of an English officer,[1730] who, in consequence of vomiting immediately after taking two ounces of laudanum, had only moderate somnolency. At other times vomiting occurs at a much later period. Pyl, in his Essays and Observations, gives a case in which, some hours after thirty grains were swallowed, vomiting took place spontaneously, and recurred frequently afterwards; in the same paper is an account of another case by the individual himself, who attempted to commit suicide by taking a large dose of laudanum, but was disappointed in consequence of the poison being spontaneously vomited after the sopor had fairly set in;[1731] and a similar case is related by M. Mascarel, where, after seven ounces of Sydenham’s laudanum had been taken, vomiting occurred spontaneously, and was followed only by inconsiderable stupor.[1732]—Vomiting is a common enough symptom after the administration of emetics, or subsequent to the departure of the somnolency.[1733] The _ordinary duration_ of a fatal case of poisoning with opium is from seven to twelve hours. Most people recover who outlive twelve hours. At the same time fatal cases of longer duration are on record: Réaumur mentions one which proved fatal in fifteen hours,[1734] Orfila another fatal in seventeen hours,[1735] Leroux another fatal in the same time,[1736] Alibert another fatal in nearly twenty-four hours.[1737] An instance has even been related, which appeared to prove fatal not till towards the close of the third day;[1738] but the whole course of the symptoms was in that case so unusual, that some other cause must have co-operated in occasioning death. Sometimes, too, death takes place in a shorter time than seven hours; six hours is not an uncommon duration; I once met with a judicial case, which could not have lasted above five hours; an infirmary patient of my colleague, Dr. Home, died in four hours; in the 31st volume of the Medical and Physical Journal, there is one which proved fatal in three hours.[1739] This is the shortest I have read of. The dose of opium requisite to cause death has not been determined. Indeed it must vary so much with circumstances, that it is almost vain to attempt to fix it. Pyl relates a case, quickly fatal, where the quantity taken was 60 grains;[1740] Lassus an instance of death from 36 grains;[1741] Wildberg has related a fatal case caused by little more than half an ounce of the Berlin tincture,[1742] which contains the soluble matter of forty grains; and Mr. Skae has mentioned a case fatal in about thirteen hours, where the dose seems to have been well ascertained not to have exceeded half an ounce of common laudanum, or about twenty grains of opium.[1743] Dr. Paris, without quoting any particular fact, says four grains may prove fatal.[1744] I should have felt some difficulty in admitting this statement, as I have repeatedly known persons, unaccustomed to opium, take three or four grains without any other effect than sound sleep. But I have been favoured with the particulars of a case by Mr. W. Brown of this city, where a dose of four grains and a half, taken by an adult along with nine grains of camphor, was followed by the usual signs of narcotism, and death in nine hours. The man took the opium for a cough at seven in the morning; at nine his wife found him in a deep sleep, from which she could not rouse him; nothing was done for his relief till three in the afternoon, when Mr. Brown found him labouring under all the usual symptoms of poisoning with opium, contracted pupils among the rest; and death ensued in an hour, notwithstanding the active employment of remedies. On examining the body no morbid appearance was found of any note except fluidity of the blood,—a common appearance in those who have died of the effects of this drug. It is more important than may at first sight be imagined to acquire an approximative knowledge of the smallest fatal dose. For, in consequence of the dread entertained of opium by many unprofessional persons, it is currently believed to be much more active than it is in reality; and instances of natural death have been consequently imputed to medicinal doses taken fortuitously a short time before. The facts stated above comprehend the only precise information I have been able to collect as to the smallest fatal doses in adults. I may add some farther observations, however, on the smallest fatal doses in children. Very young children are often peculiarly sensible to the poisonous action of opium, so that it is scarcely possible to use the most insignificant doses with safety. Sundeling states in general terms that extremely small doses are very dangerous to infants on account of the rapidity of absorption. This opinion is amply supported by the following cases.—An infant three days old got by mistake about the fourth part of a mixture containing ten drops of laudanum. No medical man was called for eleven hours. At that time there was great somnolency and feebleness, but the child could be roused. The breathing being very slow, artificial respiration was resorted to, but without advantage: the child died in twenty-four hours, the character of the symptoms remaining unchanged to the last. At the inspection of the body, which I witnessed, no morbid appearance was found.—Of the same kind was a case communicated to me by Dr. Simson of this city, where the administration of three drops of laudanum in a chalk mixture, for diarrhœa, to a stout child fourteen months old, was followed by coma, convulsions, and death in about six hours. Dr. Simson satisfied himself, as far as that was possible, that the apothecary who made up the mixture did not commit a mistake.—Dr. Kelso of Lisburn met with a similar case in an infant of nine months, who died in nine hours after taking four drops.[1745]—My colleague, Dr. Alison, tells me he has met with a case where an infant a few weeks old died with all the symptoms of poisoning with opium after receiving four drops of laudanum, and that he has repeatedly seen unpleasant deep sleep induced by only two drops.—These remarks being kept in view, it will, I suspect, be difficult to go along with an opinion against poisoning expressed by a German medico-legal physician in the following circumstances. A child’s maid, pursuant to a common but dangerous custom among nurses, gave a healthy infant, four weeks old, an anodyne draught to quiet its screams. The infant soon fell fast asleep, but died comatose in twelve hours. There was not any appearance of note in the dead body; and the child was therefore universally thought to have been killed by the draught. But the inspecting physician declared that to be impossible, as the draught contained only an eighth of a grain of opium and as much hyoscyamus.[1746] In the first edition of this work an opinion was expressed to the same purport. But the facts stated above throw doubt on its accuracy, and rather show that the dose was sufficient in the circumstances to occasion death. A very important circumstance to attend to in respect to the dose of opium required to prove fatal is the influence of constitutional circumstances in rendering this drug unusually energetic. In some persons this peculiar anomaly exists always, even during a state of health. Thus, I am acquainted with a gentleman on whom seven drops of laudanum act with great certainty as a hypnotic. In such a one doses, which are safely taken by many, might prove dangerous. It is more usual, however, to meet with this anomaly in the course of some diseases. These have not yet been satisfactorily indicated. I have several times, however, met with unusually energetic action from medicinal doses in elderly persons affected with severe habitual catarrh; and in one instance death occurred after a dose of twenty-five drops in the advanced stage of acute catarrh supervening on its chronic form, the symptoms being those of poisoning with opium, succeeding apparently a state of comfortable sleep.—A case seemingly of the same nature, where the dose was fifteen drops of Battley’s Sedative Liquor, occurred at Islington in 1841. An elderly lady, in delicate health, and affected severely with asthma, which for ten days prevented her from sleeping, got from a neighbouring druggist a draught of Battley’s solution, syrup, and camphor-mixture. Next morning she was found insensible and livid in the face, with cold extremities and contracted pupils; and she died about twelve hours after taking the draught. There was no sign of natural disease in the dead body to account for death. The druggist was absurdly blamed for giving such a dose to a frail old lady; for the dose was not more than would be generally given in such circumstances. This case was communicated to me by the druggist in question.—Another of the like kind has been communicated to me by Mr. Garstang of Clitheroe. An elderly female, long subject to severe cough, having enjoyed a comfortable night’s rest after a dose of a preparation containing half a grain of opium, took in the morning the equivalent of two grains and a half, or three grains at the utmost, and fell asleep soon after. In no long time, her husband, alarmed because he could not rouse her, sent for Mr. Garstang, who found her husband labouring under all the symptoms of poisoning with opium; and, notwithstanding active treatment, she died six hours after the second dose. Her husband took half a grain with her the evening before, but experienced no effect from it at all. Not the slightest ground could exist in this case for suspecting either foul play or pharmaceutic error.—As a farther illustration, the following incident deserves notice, which occurred last year in London, and was communicated to me by Dr. G. Johnson, a former pupil. A little girl, five years and a half old, affected with violent cough, got a mixture containing opium, which was repeated six, thirteen, and twenty-six hours afterwards. She slept soundly after each dose, and awoke readily after the first three; but after the fourth she had more stupor and much uneasiness; in which state, but with at least one interval of sensibility, she died in nine hours more, or thirty-five hours after the first dose. According to the prescriber’s intention, the child ought to have taken only two minims of laudanum in all; but, according to a rough analysis by Mr. Alfred Taylor, each dose contained an eighth of a grain of opium, or a trifle more. In either view it is impossible that doses so small, and so distant, could produce these effects in ordinary circumstances. Such cases are important in several respects, but especially because they naturally give rise to suspicions of an over-dose of opium having been incautiously given, and thus to misrepresentations injurious to the druggist or medical attendant. In the last case a Coroner’s Jury brought in the preposterous verdict, that death was caused by “too much opium ordered without due instructions.” It is scarcely necessary to add, that the dose required to prove fatal is very much altered by habit. Those who have been accustomed to eat opium are obliged gradually to increase the dose, otherwise its usual effects are not produced. Some extraordinary, but I believe correct information on this subject, is contained in the confessions of an English opium-eater. The author took at one time 8000 drops daily, or about nine ounces of laudanum. An important topic relative to the effects of opium on man is its operation on the body when used continuously in the manner practised by opium-eaters. This subject was brought forcibly under my notice in 1831, in consequence of a remarkable civil trial, in which I was concerned as a medical witness,—that of Sir W. Forbes and company against the Edinburgh Life Assurance Company. The late Earl of Mar effected insurances on his life to a large amount while addicted to the vice of opium-eating; which was not made known at the time to the insurance company. He died two years afterwards of jaundice and dropsy. The company refused payment, on the ground that his lordship had concealed from them a habit which tends to shorten life; and Sir W. Forbes and company, who held the policy of insurance as security for money lent to the earl, raised an action to recover payment. In consequence of inquiries made on this occasion, I became for the first time aware of the frequency of the vice of opium-eating among both the lower orders and the upper ranks of society; and at the same time satisfied myself, that the habit is often easily concealed from the most intimate friends,—that physicians even in extensive practice seldom become acquainted with such cases,—that the effects of the habit on the constitution are not always what either professional persons or the unprofessional would expect,—and generally that practitioners and toxicologists possess little or no precise information on the matter. In what is about to be offered on the subject, some facts will be stated which appear to me interesting, and may induce others to contribute their knowledge towards filling up so important a blank in medico-legal toxicology. The general impression is, that the practice of opium-eating injures the health and shortens life. But the scientific physician in modern times has seen so many proofs of the inaccuracy of popular impressions relative to the operation of various agents on health and longevity,[1747] that he will not allow himself to be hastily carried along in the present instance by vague popular belief. The general conviction of the tendency of opium-eating to shorten life has obviously been derived in part from the injurious effects which opium used medicinally has on the nervous system and functions of the alimentary canal,—and partly on the reports of travellers in Turkey and Persia, who have enjoyed opportunities of watching the life and habits of opium-eaters on a great scale. The statements of travellers, however, are so vague that they cannot be turned to use with any confidence in a scientific inquiry. Chardin, one of the earliest (1671) and best of modern travellers in Turkey, merely says the opium-eater becomes rheumatic at fifty, and “never reaches an extreme old age;”[1748] and his successors have seldom been more precise,—no one having given information as to the diseases which it tends to engender. By far the greater number of authorities, however, agree in representing the practice to be hurtful. Mr. Madden, a recent and professional authority, even alleges that it is very rare for an opium-eater at Constantinople to outlive his thirtieth year, if he began the practice early. On the other hand, a few late observers deny altogether the accuracy of these statements. To this number belongs Dr. Burnes of the Bombay army; whose opinion is worthy of notice, because he had ample opportunities of observation during his residence in Cutch and at the Court of Sinde for several years prior to 1831. From what he there witnessed, Dr. Burnes is inclined to think “it will be found in general that the natives do not suffer much from the use of opium,”—that “this powerful narcotic does not seem to destroy the powers of the body, nor to enervate the mind to the degree that might be imagined.”[1749] Dr. Macpherson of the Madras army, who had occasion to observe the effects of the parallel practice of opium-smoking in China, coincides in opinion with Dr. Burnes. He says, “were we to be led away by the popular opinion that the habitual use of opium injures the health and shortens life, we should expect to find the Chinese a shrivelled, emaciated, idiotic race. On the contrary, although the habit of smoking opium is universal among rich and poor, we find them to be a powerful, muscular, and athletic people, and the lower orders more intelligent and far superior in mental acquirements to those of corresponding rank in our own country.”[1750] The familiar effects of the medicinal use of opium in disordering the nervous system and the digestive functions constitute a better reason, than the loose statements of eastern travellers, for the popular impression of the danger of its habitual and long-continued use. Yet this consideration ought not to be allowed too much weight; because the functions of the nervous system and of digestion may be deranged by other causes, for example by hysteria, without necessarily and materially shortening life. It is desirable therefore to appeal if possible to precise facts. The following is a summary of twenty-five cases, the particulars of which I have obtained from various quarters. The general result rather tends to throw doubt over the popular opinion.—1. A lady about thirty, in good health, has taken it largely for twenty years, having been gradually habituated to it from childhood by the villany of her maid, who gave it frequently to keep her quiet. 2. A female who died of consumption at the age of forty-two, had taken about a drachm of solid opium for ten years, but had given up the practice for three years before her death, and led in other respects a licentious life from an early age. 3. A well-known literary author, about sixty years of age, has taken laudanum for thirty-five years, with occasional short intermissions, and sometimes an enormous quantity, but enjoys tolerable bodily health. 4. A lady, after being in the practice of drinking laudanum for at least twenty years, died at the age of fifty,—of what disease I have been unable to learn. 5. A lady about fifty-five, who enjoys good health, has taken opium many years, and at present uses three ounces of laudanum daily. 6. A lady about sixty gave it up after using it constantly for twenty years, during which she enjoyed good health; and subsequently she resumed it. 7. Lord Mar after using laudanum for thirty years, at times to the amount of two or three ounces daily, died at the age of fifty-seven of jaundice and dropsy; but he was a martyr to rheumatism, and besides lived rather freely. 8. A woman, who had been in the practice of taking about two ounces of laudanum daily for very many years, died at the age of sixty or upwards. 9. An eminent literary character, who died about the age of sixty-three, was in the practice of drinking laudanum to excess from the age of fifteen; and his daily allowance was sometimes a quart of a mixture consisting of three parts of laudanum and one of alcohol. 10. A lady, who died lately at the age of seventy-six, took laudanum in the quantity of half an ounce daily for nearly forty years. 11. An old woman died not long ago at Leith at the age of eighty, who had taken about half an ounce of laudanum daily for nearly forty years, and enjoyed tolerable health all the time. 12. Visrajee, a celebrated Cutchee chief, mentioned by Dr. Burnes, had taken opium largely all his life, and was alive when Dr. Burnes drew up his Narrative, at the age of eighty, “paralyzed by years, but his mind unimpaired.”[1751] For the particulars of the remaining cases I am indebted to Dr. Tait, surgeon of police in this city. 13. M. C., a ruddy, healthy-looking woman, sixty years of age, has taken laudanum for twenty-five years to the extent of half an ounce daily in a single dose. 14. M. H., a flabby, dissipated-looking woman of thirty-six, has taken for ten years thirty grains of opium daily in three doses. 15. M. T., a widow, forty-eight years of age, who takes twice daily a dose of one fluidrachm of laudanum, and has done so for fourteen years, cannot observe any permanent injury except diminution of appetite. 16. Mrs. G., aged twenty-four, has taken a single dose of sixty drops regularly at bed-time for five years, and has not suffered in health in any respect, except that she is costive. 17. F. S., a thin, sallow woman of forty-six years of age, has taken a fluidrachm of laudanum three times a day for ten years, cannot take food without it, but is so well as to be able to get up regularly at six in the morning. 18. H. S., a shrivelled old-looking woman, who for thirty-eight years had taken daily towards a drachm of opium in one dose, and who latterly was strong, lively, and of good appetite, died recently at the age of sixty-nine. 19. Mrs. S., who has taken about a scruple of opium for twenty-one years, is a tall, active, old-looking woman of fifty-seven, enjoys good health when she uses the opium, but suffers from an affection like delirium tremens, when she cannot get her usual quantity. 20. M. A., aged thirty-one, has taken half a drachm of opium daily in two doses for ten years, was a thin, drunken, starved-looking prostitute some years ago, but, having reformed her ways, is now “a fine-looking, bouncing woman,” younger in appearance than formerly, and not liable to any suffering either before or after her doses, except that she cannot take food without them. 21. Miss M., who has taken ten grains of opium three times a day for five years, is a healthy, florid young woman of twenty-seven, liable to costiveness, and, when without her opium, to languor and want of appetite, but otherwise free of complaint. 22. Mrs. ——, a plump, hale-looking old lady of seventy, has taken opium for six and twenty years, and for some years to the extent of a drachm daily in two doses. She thinks her health improved by it, and has suffered no inconvenience except merely costiveness, and always aversion to food till she gets her dose. 23. J. B., aged 23, has taken laudanum since she was fourteen, and some time past to the amount of an ounce or ten drachms in three or four doses daily. She has only menstruated twice since first using the laudanum, has bilious vomiting once a month, and looks older than her years, but is otherwise quite healthy, and has two children. 24. Mrs. M’C., a ruddy young-looking woman of forty-two, has taken opium during two years for cough and pain in the stomach, latterly to the extent of ten grains twice a day. She has never menstruated since, but has enjoyed better health, and in particular has a good appetite after her dose, and has got entirely quit of a former tendency to constipation. 25. An army officer’s widow, fifty-five years old, healthy and young-looking, although subject to costiveness and rather defective appetite, has taken laudanum for eleven years, and latterly opium to the extent of fifteen grains morning and evening. These facts tend on the whole rather to show, that the practice of eating opium is not so injurious, and an opium eater’s life not so uninsurable, as is commonly thought; and that an insured person, who did not make known this habit, could scarcely be considered guilty of concealment to the effect of voiding his insurance. But I am far from thinking,—as several represent who have quoted this work,—that what has now been stated can with justice be held to establish such important inferences; for there is an obvious reason, why in an inquiry of this kind those instances chiefly should come under notice where the constitution has escaped injury, cases fatal in early life being more apt to be lost sight of, or more likely to be concealed. Meanwhile, insurance companies and insurance physicians ought to be aware, that not a few persons in the upper ranks of life are confirmed opium-eaters without even their intimate friends knowing it. And the reason is, that at the time the opium-eater is visible to his friends, namely, during the period of excitement, there is frequently nothing in his behaviour or appearance to attract particular attention. From the information I have received, it appears that the British opium-eater is by no means subject to the extraordinary excitement of mind and body described by travellers as the effect of opium-eating in Turkey and Persia; but that the common effect merely is to remove torpor and sluggishness, and make him in the eyes of his friends an active and conversible man. The prevailing notions of the nature of the excitement from eating opium are therefore very much exaggerated. Another singular circumstance I have ascertained is, that constipation is by no means a general effect of the continued use of opium. In some of the cases mentioned above no laxatives have been required; and in others a gentle laxative once a week is sufficient. In the civil suit regarding Lord Mar’s insurances, the insurance company was at first found not entitled to refuse payment,—not, however, on the ground that the habit of opium-eating is harmless to longevity,—but chiefly on a technical ground, implying that they did not make inquiry into his habits with the care usually observed by insurance companies, and were therefore to be understood as accepting the life at a venture. A new trial was granted by the court on the ground of the judge’s charge having been not according to evidence; but on this occasion the parties compromised the case.[1752] The previous remarks on the symptoms of poisoning with opium in man have been confined to its effects when swallowed. But it was mentioned under the head of its mode of action, that this poison has been known to act with energy upon animals through every channel by which it can be introduced into the system. It is natural to expect that the same will be the case with man also. The only other modes in which poisoning with opium is reported to have been produced in man, besides administration by the mouth, have been by injections into the anus, by application to the skin deprived of its cuticle, perhaps even also to the unbroken skin, and by its introduction into the external opening of the ear. In the Journal de Chimie Médicale, an instance is shortly noticed of a lady who was poisoned by the administration of too strong an anodyne injection prepared by herself from fresh poppy-heads. She recovered.[1753] It is generally believed in France that opium acts more energetically through the medium of the rectum, than through the stomach. Orfila in particular has endeavoured to establish this proposition by experiments on animals, and quotations from cases recorded by some authors of its action upon man.[1754] But neither the experiments nor the quotations appear to me satisfactory; and the rule they go to support is completely at variance with the practice pursued in the medicinal administration of the drug in Britain. It is the custom to give at least twice as much in an enema as in a draught. I have given by injection, without producing more than the usual somnolency, one drachm and even two drachms by measure of laudanum, a dose which, were Orfila’s statement correct, would prove fatal. As to the action of opium through the skin when deprived of its cuticle, I am not acquainted with any fatal case of the kind, but have no doubt that such may happen. One of my friends very nearly lost his life in the way alluded to. He had applied an opium-poultice to the scrotum to allay the violent irritation caused by a blister, and fell into a state of profound sopor, which was luckily interrupted by a visitor, so that the cause was discovered before it was too late. An instance of the same kind has also been published by M. Pelletan. A child two months old very nearly perished, in consequence of a cerate containing fifteen drops of laudanum having been kept for twenty-four hours on a slight excoriation produced by a fold of the skin. When the cause of illness was discovered, the child had been for some hours almost completely insensible, with a slow, obscure pulse, and occasional convulsions.[1755] But perhaps opium may in some circumstances act even through the unbroken skin. It has certainly been often applied in this way to relieve local pain without avail. Yet on the other hand its effect is at times unequivocal; and the following incidents seem to show, that it may even prove fatal, both when the skin is healthy, and in certain diseased states of the integuments. A young dramatic writer in Paris was directed by his father, a physician, to apply over the stomach a poultice moistened with a few drops of laudanum. The patient, in order to relieve his pain more quickly, poured the whole contents of the bottle over the poultice, and soon fell into a deep sleep. Prompt assistance was obtained, but proved of no avail, and death is said to have ensued with great rapidity.[1756] A soldier affected with erysipelas of the leg, had a linseed poultice applied, which his surgeon ordered to be sprinkled with 15 drops of laudanum. Next morning the patient was found in a state of deep sopor, accompanied with convulsive twitches of the muscles of the face and limbs; and in no long time he expired. His soporose state turned the surgeon’s attention to the poultice, which he found coloured yellow and smelling strongly of opium; and on removing it he discovered that it was completely soaked with laudanum, which the attendant had carelessly poured on it to the extent of an ounce. The patient died notwithstanding all the remedies which his state called for; and the viscera were found quite healthy; but in many places the blood is said to have had a strong odour of opium.[1757] In an instance reported by M. Tournon of Bordeaux, death is supposed to have arisen from the introduction of opium into the external opening of the ear, as a remedy for ear-ache. It is possible that fatal poisoning may thus be induced by laudanum too freely and frequently renewed: but it seems very unlikely that death was owing to opium in the instance in question, since it was used in the solid form, and in the quantity of four grains; so that the dose was small, and absorption must have been very slow. The account merely states that the patient fell asleep, but his sleep was that of death.[1758] _Of the Action of Morphia, Narcotine, Codeïa, and Meconic Acid._ The action and symptoms caused by two active principles of opium, morphia, and narcotine, have been examined by many experimentalists. The action of _morphia_ is nearly the same as that of opium, but more energetic. In its solid state it has little effect, being nearly insoluble. But when dissolved in olive oil, or in alcohol, or in weak acids, it excites in animals the same symptoms as opium. Experimentalists are not yet agreed as to its power. The trial of Castaing gave rise to a physiological inquiry by three French physicians, Deguise, Dupuy, and Leuret, who assigned to it feeble properties; but more reliance is usually placed in the experiments of Orfila, who found that one part of morphia is equal in energy to two parts of the watery extract, and to four parts of crude opium. The observations I have made on the medicinal effects of morphia and its muriate, lead me to believe that half a grain is fully equal in power to three grains of the best Turkey-opium. Probably those who have observed but slight effects from it have accidentally used narcotine instead of it; for at one time they were often confounded together. On man morphia acts like opium; it produces somnolency. It was at one time thought that in medicinal doses it does not produce either the disagreeable subsequent or idiosyncratic effects of opium; Magendie made some observations to this purport;[1759] and Dr. Quadri of Naples was led to the same conclusion.[1760] Others, however, have doubted the accuracy of these authors, and opposite results appear to have been procured by some. My own experience with the muriate of morphia inclines me to concur in opinion with Magendie and Quadri. The effects of morphia on man in fatal doses have hitherto been observed in a few cases only. An instance, which was the occasion of a criminal trial at Aberdeen in 1842, has been communicated to me by Dr. Traill, who was consulted in the case on the part of the crown. A schoolmaster gave ten grains of the muriate to a girl immediately after she came out of an epileptic fit. In fifteen minutes she seemed to fall asleep; she continued in this state for some hours before it was discovered that she was in a state of stupor, from which she could not be roused; and she expired twelve hours after the poison was administered. A similar case occasioned by ten grains, and also fatal, occurred at Cheltenham in 1839. Orfila relates the particulars of the case of a young Parisian graduate, who swallowed twenty-two grains for the purpose of self-destruction. In ten minutes he felt heat in the stomach and hindhead, with excessive itchiness; in three hours and a half he had also a sense of pricking in the eyes, with dimness of vision; and in an hour more he for the first time felt approaching stupor. Half an hour afterwards, when the people of the house entered his room he could not see them, though he was sensible enough to be able to reply to their inquiries, that he lay in bed because he had not slept the night before. Soon after this he fell into a state of profound stupor and lost all consciousness. In thirteen hours he was visited by Orfila, who found him cold, quite comatose, and affected with locked-jaw; the pupils were feebly dilated, the pulse 120, the breathing hurried and stertorous, the belly tense and tympanitic; and there were occasional convulsions, with intense itching of the skin. By means of copious venesection, sinapisms, ammoniated friction, stimulant clysters, ice on the head, and acidulous drinks, he was gradually roused, so that in six hours he recognised his physician. In the subsequent night and following day he had difficult and scanty micturition, with pain in the kidneys and bladder, and difficulty in swallowing; but these symptoms went off during the second night; and on the third morning he was quite well.[1761] The itching of the skin remarked in this case is considered by M. Bally an invariable symptom of the operation of morphia even in medicinal doses.[1762] It is not, however, always produced. Another case, which occurred at Lunéville, is very remarkable in its circumstances. A young man addicted to opium-eating, but who had left off the practice for a twelvemonth, took first ten grains, and in ten minutes forty grains more of acetate of morphia. In five minutes he had excessive general feebleness and a sense of impending dissolution, which forced him to confess what he had done. In fifteen minutes more M. Castara, who describes the particulars, found him motionless, almost comatose, and breathing laboriously. The limbs were flaccid, the pupils contracted, the face and lips livid, the skin warm and moist, the pulse full and hard, and deglutition impossible. Tartar-emetic was ordered, but could not be administered. He was then bled at the arm to eighteen ounces; upon which he started as from sleep, rubbed his eyes, said every thing turned round him, and that he could not see the people present. When left to himself he quickly fell into a calm slumber; but if kept awake, he told collectedly all that happened before he became comatose. He complained chiefly of intense itching and a general sense of bruising. In an hour, by keeping him constantly roused, consciousness was almost restored, and this without vomiting having been produced, though two grains of tartar-emetic had been swallowed and three administered by the rectum. In four hours after he swallowed the poison he vomited freely and had diarrhœa. He then steadily recovered, the sleepiness continued all next day, and the itching of the skin even longer.[1763] M. Julia-Fontenelle met with a case of poisoning with this alkaloid, in consequence of its having been administered with a clyster in the form of sulphate. The subject was a child five years old, the dose five grains, the symptoms those of apoplexy, and death supervened within twenty-four hours.[1764] Another case worthy of particular mention is that of the French gentleman who was supposed to have been poisoned by Dr. Castaing. It is not a pure one, for besides the symptoms of a consumptive complaint under which he had laboured for some time, there were circumstances in his last illness which indicated the administration of other deleterious substances. About thirty-six hours before his death, however, they were exactly such as might be expected from a large dose of morphia. About five minutes after the administration of a draught by the prisoner, the gentleman was attacked with convulsions, and not long afterwards his physician found him quite insensible, unable to swallow, bathed in a cold sweat, with a small pulse, a burning skin, the jaws locked, the neck rigid, the belly tense, and the limbs affected with spasmodic convulsions. In this state he seems to have continued till his death. The only appearances found in the dead body, which bore any relation to the poison suspected, were congestion of blood and serous effusion in the vessels of the cerebral membranes. If morphia was the cause of death, it is highly probable that, besides what was administered thirty-six hours before he died, several doses were given subsequently; otherwise, from what is known of the action of opium, the narcotism could scarcely have lasted uninterruptedly for so long a period.[1765] For the following extraordinary case I am indebted to one of my pupils, Mr. Clark of Montrose: A woman took one morning by mistake ten grains of pure muriate of morphia, which had been prepared not long before by Mr. Clark in my laboratory, and was freed of codeïa. The mistake having been discovered almost immediately, means were taken to prevent any ill effects from the accident, and within half an hour after the poison was swallowed, the stomach was completely cleared by the stomach-pump. At this time she was quite sensible. But stupor quickly came on after the poison was evacuated, and deep imperturbable coma gradually formed, so that nothing could rouse her in the slightest degree except cold affusion of the head and chest, which caused faint signs of returning consciousness. Before night she expired, though all the usual remedies were resorted to. An inspection of the body was not obtained, which is much to be regretted, since without it the case is quite obscure. I do not know a single instance of fatal coma from opium where the proper remedies were resorted to before the stupor commenced; and death in such circumstances is so inconceivable, that we must ascribe the result in this case to apoplexy, either incidentally concurring, or brought on by the operation of the poison. Morphia, like opium, may occasion serous effects when too freely applied to a blistered surface. In a case related by M. Dupont, four-tenths of a grain of acetate of morphia, applied to a blister on the side, caused in twenty minutes dimness of vision, vomiting, and delirium; and though it was then removed, the patient had afterwards continued vomiting, dilated pupils, and great feebleness of the pulse. Recovery took place, but the patient was not quite free of incoherence next day.[1766] The dose here was so small, and the symptoms were so unlike the usual effects of morphia, that doubts arise whether the case was really one of poisoning. The effects of _narcotine_ have been examined experimentally by Magendie and Orfila; but their results do not coincide. According to Orfila it is not easy to poison dogs with it, as it excites vomiting and is discharged. But when the gullet is tied, the animal dies in two, three or four days, without any remarkable symptom but languor and hard breathing.[1767] In these experiments it was dissolved in olive oil; it does not act at all in the solid state. Magendie found that it produces in dogs a state like reverie, accompanied with convulsions. They lie still except when convulsed, and they are apparently asleep or dreaming; but they are really alive to external objects, and even in a state of acute irritability. In short, he considers the symptoms to constitute an aggravated form of the subsequent and idiosyncratic effects caused by opium on man. Vinegar, he says, destroys altogether the poisonous properties of narcotine. According to Orfila it only weakens them. Muriatic acid would seem to annihilate them entirely; for Orfila found no effect in dogs from forty grains dissolved in water with the aid of muriatic acid; and Bally gave sixty grains in like manner to a patient without injury.[1768] Forty grains dissolved by sulphuric acid, proved fatal to a dog in twenty-four hours.[1769] Narcotine, like other narcotic poisons, is more powerful when introduced at once into the blood, but produces nearly the same effects as when it is swallowed. Orfila found that a single grain was as powerful through the former, as eight grains through the latter channel.[1770] Dieffenbach observed that half a grain dissolved in water by means of a drop or two of hydrochloric acid killed cats in five minutes when injected into a vein, and always produced congestion within the head, and extravasation on the surface of the cerebellum. A remarkable circumstance observed in the course of his experiments was, that leeches, applied to a rabbit under the influence of narcotine, died immediately in convulsions; and that a portion of the blood of the same rabbit when injected into the vein of another produced drowsiness, languor, and pandiculation for nearly a day.[1771] The effects of narcotine on man have not been much inquired into. From the only researches on the subject I have yet seen, those of Dr. Wibmer of Munich, it appears to be but a feeble poison. He found by experiment on himself, that two grains dissolved in olive oil produced merely slight transient headache; that eight grains dissolved by means of muriatic acid had no effect at all; and that the same quantity of solid narcotine occasioned temporary headache, and in twenty-eight hours a singular state of excitement, with trembling of the hands, restlessness, and inability to fix the thoughts on any object. These effects went off in a few hours.[1772] The effects of _codeïa_ have been examined by Dr. Kunkel. He found that twelve grains, dissolved in water and introduced into the stomach, killed a rabbit in three minutes; that six grains in solution when injected into the cellular tissue occasioned death in little more than two hours; that the same quantity administered by the mouth sometimes had little effect; that when given in powder its action was very feeble; and that the symptoms were excitement of the pulse, convulsions, and tetanus, without any tendency to sopor or somnolency.[1773] Hence codeïa is conceived to be a stimulant of the nervous system, and consequently the cause of the excitant effects sometimes produced by opium. It may be doubted, however, whether its proportion in opium is sufficient for explaining these effects. _Meconic acid_ is inert. Sertuerner, indeed, thought the meconate of soda acted as a powerful poison in some experiments made on himself and on dogs; but more careful researches have since proved that he was misled by some error. Sömmering found that ten grains of meconic acid or meconate of soda had no effect whatever on dogs.[1774] Subsequently, in consequence of two people having died suddenly at Turin after taking each a grain of the acid, some careful experiments were made by Drs. Feneglio and Blengini, who gave eight grains to dogs, crows, and frogs, and four grains to various men, without remarking any injurious effects whatever.[1775] The _distilled water_ of opium was formerly considered an active poison; but Orfila found it nearly or altogether inert. Two pounds introduced into the stomach of a dog, and two ounces and a half injected into a vein, had no effect whatever.[1776] SECTION III.—_Of the Morbid Appearances caused by Opium._ In discussing this subject the appearances in the best marked cases will be first noticed; and then some account; will be given of the variations to which they are liable. In Knape’s Annals there is a good example of the most aggravated state of the appearances left by opium. It is the case of an infant who was killed in the course of a night by a decoction of poppy-heads. There was much lividity over the whole back part of the body. All the sinuses and vessels of the brain were gorged with fluid blood; and a good deal of serosity was found in the ventricles and base of the skull. The pharynx was red. The lungs were distended, and so gorged with fluid blood, that it ran out in a stream when they were cut. The cavities of the heart contained the same fluid blood. There was some redness in the villous coat of the stomach and intestines; and poppy-seeds were found in the stomach. Although the body had been kept only two days in the month of February, the belly emitted a putrid odour when it was laid open.[1777] In commenting upon these appearances, it may be first remarked, that turgescence of the vessels in the brain, and watery effusion into the ventricles, and on the surface of the brain, are generally met with. Dr. Bright mentions an instance where unusual turgescence was found, and on the surface of the brain a spot of slight ecchymosis as big as a crown piece.[1778] I have seen turgescence of vessels and serous effusion in one instance to a considerable extent: each ventricle contained three drachms of fluid, the arachnoid membrane on the surface of the brain was much infiltered, and the vessels both in the substance and on the surface of the brain were considerably gorged with blood. But congestion and effusion are by no means universal: in a case I examined judicially in November, 1822, which proved fatal in about seven hours, there was neither unusual congestion nor effusion. In the remarks on the diseased appearances caused by the narcotics generally, it was observed that extravasation of blood is a very rare effect of opium. A good example of the kind, however, is related by Mr. Jewel of London. It was the case of a young married female, who died eight hours after taking two ounces of laudanum. Several clots were found in the substance of the brain, one of which, in the anterior right lobe, was an inch long.[1779] A similar case, which occurred to Dr. Elliotson, has been mentioned already at p.