Central Venous Catheterization for Parenteral Nutrition
FRANK T. PADBERG, JR., M.D., JOHN RUGGIERO, B.S.,GEORGE L. BLACKBURN, M.D., PH.D., BRUCE R. BISTRIAN, M.D., PH.D.
To define the risks associated with central venous catheteriza-tion for total parenteral nutrition (TPN) 3291 patient daysof this therapy, delivered by an established nutrition supportteam, were evaluated. One hundred and seventy-five cathetersplaced in 104 patients were reviewed over an 18 monthperiod. Positive cultures were reported on 11 cannulae fora 6.4% incidence of colonization; five catheters (2.8%)were considered septic. Pleural or mediastinal compli-cations of subclavian or internal jugular venipuncture oc-curred in eight patients (4.8%). Misdirection of the cathetertip occurred in 11.5% of insertions. Five patients (4.8%)had clinically apparent thrombosis in the superior vena cava,innominate and/or subclavian veins during hospitalization;four others had evidence of thrombosis at autopsy examina-tion, giving an incidence of 8.7% in the entire series. No deathdirectly resulted from the use of this therapy. Compliancewith a rigid protocol by an experienced team can allow safeand effective use of central venous catheters and parenteralnutrition therapy.
S INCE DUDRICK'S LANDMARK PUBLICATION overa decade ago,1 total parenteral nutrition (TPN)
has gained wide acceptance as a valuable adjunct inthe care of critically ill patients. A multitude ofserious rmietabolic complications can arise from TPN;these are related to the composition of solutions in-tended to be nutritionally complete, and rangefrom hyperglycemic coma to vitamin or mineraldeficiencies.2 Central venous access is a necessitydue to the high osmolarity of the TPN solutions,which present problems related to the establishmentand maintenance of central venous catheters.Ryan et al. presented a concise review of in-
fectious and mechanical complications associated withvenous catheterization for TPN.3 In that seriescatheter-related sepsis occurred in 7.0% of the catheters
Supported by Grant No. GM-22691 and GM-24401 awarded by theNational Institute of General Medical Sciences, DHEW. Dataorganization and analysis was performed on the PROPHET system,sponsored by the Chemical/Biological Information Handling Pro-gram, National Institutes of Health.
This is article 680 from the Cancer Research Institute of the NewEngland Deaconess Hospital.
Reprint requests: George L. Blackburn, M.D., Ph.D., CancerResearch Institute, 194 Pilgrim Road, Boston, Massachusetts 02215.
Submitted for publication: October 13, 1980.
From the Nutrition Support Service and Nutrition!Metabolism Laboratory, Cancer Research Institute,New England Deaconess Hospital, Harvard Medical
School, Boston, Massachusetts
and was correlated with more frequent violations ofa standard protocol for line care; eight of 25 cultureswere positive for fungal organisms. Colonization wasnot described per se, but it can be inferred that itoccurred in 8.4% of the patients. Pleural and medias-tinal complications occurred in 2.5% of their patients,with one death directly attributed to catheterization.Deitel4 noticed a 24% incidence of catheter tip mis-placement following subclavian venipuncture, but didnot localize this to one side or the other.The reported incidence of fungal infections has
fallen during the past several years. Maki5 hasrecently characterized the incidence and theoreticalbasis of intravenous infections; the predominantagents normally are inhabitants of the skin. The im-plication is that these should be well controlled byclose monitoring and fastidious skin care at theinsertion site.
Occult venous thrombosis was noticed by Ryanet al.3 at an incidence of 4%; clinical subclavian orvena caval thrombosis was not observed in their series.
Materials and Methods
MethodologyThe hospital records and radiographs of 104 con-
secutive patients who received TPN over an 18month period were reviewed by a physician. Par-ticular investigation was directed to determining acatheter's type, its site of insertion, the length oftime it remained in situ, the mechanical and in-fectious complications of its placement, and the pres-ence of venous thrombosis. Similar data were recordedfor all central venous catheters inserted concomitantlyfor other purposes in the study population. Allunsuccessful attempts at percutaneous central place-ment were noticed. Serial chest radiographs were
CENTRAL VENOUS CATHETERIZATION-TPN 265reviewed over the entire period of each patient'scannulation, providing a unique documentation ofeach catheter's history. Profiles of the patients'diagnoses and courses were recorded, but no attemptswere made to describe the metabolic aspects of theirnutritional support.
Protocol
A standard protocol was followed with each place-ment. All catheters inserted specifically for deliveryof TPN were placed, electively, at the bedside bymembers of the nutrition support service. A seniorfellow or staff physician was present at each insertionand either supervised or accomplished each catheterplacement. After free flow of blood was demon-strated, isotonic fluids were infused slowly, and achest radiograph obtained. Upon verification of properplacement, appropriate solution orders were writtenby the Nutrition Support Service.
Infraclavicular subclavian vein cannulation is pre-ferred for nutritional catheters at the New EnglandDeaconess Hospital. The internal jugular vein servesas a reasonable secondary site. Severe coagulationdefects are considered a contraindication to per-cutaneous venipuncture in these areas; central venousaccess is achieved by cut-down, percutaneous ante-cubital cannulation, or by infraclavicular catheriza-tion following replacement of the necessary pro-coagulants (i.e., fresh frozen plasma, or platelets).
Dressing Procedure
The patients were closely monitored throughouttheir courses, including daily physician visits. The"hyperalimentation nurses" replaced occlusive dress-ings on Monday, Wednesday, and Friday. The skin wascleansed mechanically using acetone, and povidone-iodine ointment was applied. The catheters involved inthis study were respected throughout the hospital andwere not used for other purposes without clearancefrom the Nutrition Support Service; however, certainextraordinary situations necessitating exceptions inthis policy were permitted.On a few occasions, a previously placed catheter
was taken over as a TPN line and thereafter wasstrictly preserved for nutrition. In addition, twotherapeutic procedures could be considered theoreticviolations of this protocol, but both were carriedout by the nutrition support team according todefined guidelines. Intravenous fat emulsions wererun "piggyback" onto the TPN line; and, onoccasion, fluids were delivered only during a portionof each day (cyclic hyperalimentation).6 With cyclicTPN, glucose administration was limited to a fraction
TABLE 1. Population (104 Patients Treated ov'er 18 Months)
NumberPatients Per Cent
Diabetes mellitus 58 56Septic during hospitalization 55 53Malignant disease 44 42Known to have died 42 40Congestive failure 33 32
of a 24 hour period and a heparinthe remainder of the period.
lock placed for
Infection and Thrombosis
On occurrence of unexplained fever, a bloodculture would be obtained through the catheter; and ifthe patient's temperature remained both elevated andunexplained the following day, the cannula would beremoved. In cases where recatherization could beparticularly hazardous, a guide-wire was used tochange the catheter and culture its tip.
Catheter-related infectious complications were iden-tified as colonization if a catheter tip culture waspositive; or, in the absence of a tip culture, if ablood culture obtained through the catheter waspositive, and concomitant peripheral blood cultureswere either negative or unavailable. Catheter-relatedsepsis was then defined as a colonized catheterassociated with a systemic bacteremia (documentedby peripheral blood culture with the same organism).A decrease in the patient's temperature concomitantwith removal of a catheter was useful in confirmingsuspected catheter sepsis, but was not considereddiagnostic. A positive culture of the skin at theinsertion site was not accepted as documentation ofcatheter colonization.A diagnosis of major venous thrombosis was ac-
cepted on the basis of contrast venograms or clearlyevident physical findings. Although failure to advancea catheter into proper position may suggest thisproblem, it was not considered valid as a diagnosticcriterion.
Results
Population (Table I)
The patient population at the NEDH is that of atertiary care center and is served by the general staff,Lahey Clinic, Overholt Thoracic Clinic, and JoslinDiabetes Clinic. Fifty-five of the patients requiringcentral venous nutritional support had sepsis, or haddemonstrated bacteremia during their period of hos-pitalization. Forty-two of the 104 patients are knownto have died; of those who died while in the hospital,
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PADBERG AND OTHERS
19 patients had postmortem examinations. Fifty-eight patients were diabetic (in addition to obviousclinical diabetes our definition included those notknown to be diabetic who required supplementalinsulin while on TPN). A malignant process wasresponsible for the referral in 44 cases. Congestiveheart failure on clinical grounds was present in 33patients. The average age of the patients was 57 years.Thus, the population is unique and seriously ill, withmany cases of chronic disease and multiple-organfailure.
Catheters
The great majority of the insertions were sub-clavian, and performed with a standard eight inch,16-gauge polyvinylchloride catheter. During the 18months, 323 central catheters were placed. Of these,175 were involved in the administration of parenteralnutrition. There were 145 subclavian and 20 internaljugular venipunctures performed by the nutritionservice. Approximately three out of every five cathe-ters were inserted on the right side (Table 2). Thissame ratio was observed in terms of the number ofcatheter days. The internal jugular vein was in-frequently used for nutritional purposes. Centralvenous catheters, for purposes other than feeding,were placed in essentially equal numbers between thesubclavian and internal jugular veins. The antecubitalfossa was occasionally used for central venous pres-sure catheter placement, and on one occasion for TPN.Those catheters not constructed of polyvinylchlorideincluded five of silicone elastomer and 19 of heparin-impregnated hydrophilic polymers.7 The average TPNcannula remained in place for 19 days. In comparing theaverage duration in situ of the various catheter ma-
terials or the different sites of insertion, no significantdifferences were observed (Table 2).
Complications of Placement
Of the more serious complications reported in theliterature, pneumothorax, hemothorax, and medias-tinal hematoma are represented here. Although lessdramatic, improperly placed catheter tips and un-
successful venipunctures were not infrequent. There
were no air or catheter emboli and no lymphaticfistulas, nor were there any catheter-related deaths.The incidence of major complications from catheter
placement in this series was 4.8%-eight of 165attempted subclavian or internal jugular catherizations.There were five pneumothoraces, for an incidence of3.0%. Two of these resolved without chest tubes.
Catheter misdirection was a fairly common problemoccurring in 19 out of 165 insertions (11.5%). Therewere 13 subclavian catheters whose tips initiallyterminated in the internal jugular vein; ten of thesewere from the right. Four catheters coiled in the veinand required straightening. Two right subclaviancatheters terminated in the left innominate or theleft subclavian veins.There were 20 unsuccessful attempts at cannulation.
In the majority of these patients, a later attemptwas usually successful, although the site may havevaried. In only one patient was a peripheral nutritionalregimen established, due to failure to achieve centralvenous cannulation. No one choice of site wasparticularly prone to result in failure.
Catheters and InfectionOf the 175 catheters used to deliver 3291 days of
TPN, there were 11 with positive cultures, for anincidence of 6.4%. Five of the catheters (2.8%) werebelieved to be a source of sepsis-one occurrenceof septicemia for every 658 catheter days. Fifty-fiveper cent of the patients were septic or had demon-strated bacteremia from other sources.
Forty-one catheters were removed for suspicion ofsepsis; of these, six (15%) had positive cultures.The earliest positive culture was observed at threedays. All but two of these catheters were colonizedwith staphylococci (six coagulase negative and threecoagulase positive). The exceptions were Serratialiquifaciens and diptheroids species.One of the 11 catheters was the only femoral TPN
catheter in this series. Two of the remaining catheterswere internal jugular, and the remainder subclaviancatheters.
Fourteen of the 175 catheters were inserted by otherservices for nonfeeding purposes, and were "takenover" by the nutrition support service. Two of these
TABLE 2. Distribution of Catheters Used for Delivery of TPN
Subclavian Internal Jugular Other Totals Catheter Days Per Cent Average Duration*
were eventually colonized, for an incidence of 14%in this rather small group. There were 20 patients whohad their TPN delivered via a cycled regimen; 22more received Intralipidg "piggy back" into theirTPN lines. Three catheters from each group returnedpositive cultures (15% and 14%, respectively), butthese patients also had a number of other complicatingfactors predisposing them to colonization.
Venous Thrombosis
There were nine patients with indwelling venous
devices who developed venous thrombosis, for an
incidence of 8.6%. Five of these patients presentedclinical evidence of thrombosis. Four of the patientspresented, initially, with left subclavian thromboses,two of which progressed to superior vena cavalthromboses. The fifth patient also had thrombosis ofthe superior vena cava, but did not have unilateralfindings.Four other patients were shown to have thrombosis
at autopsy examination. Two of these had muralthrombi noted in the superior vena cava; one patienthad undergone cardiac surgery, and both patients,had required at least seven days of pulmonary arterialmonitoring.Another patient had a right subclavian catheter
misplaced into her left subclavian vein. She receivedseveral weeks of TPN via left subclavian catheters,both preceding and following this catheter. At autopsyexamination, an organizing thrombus was identifiedin the subclavian vein; it had not been recognizedclinically and was not occlusive.The fourth patient represented the only experience
with a femoral catheter. He developed an iliofemoralthrombus and had several positive catheter culturesas well, emphasizing the necessity to avoid this site.
Discussion
Delivery of total parenteral nutrition is safe andhas provided a significant therapeutic advance, sinceits clinical introduction. The morbidity and mortalityrates associated with insertion and maintenance of theaccess system can strongly influence the acceptabilityof this treatment. The most significant of theseproblems relates to catheter placement, infection,and venous thrombosis.
Catheter Placement
The potential threats of major pleural and medias-tinal complications are self-evident. The incidence ofthese has been inversely correlated with experiencein technique, and positively correlated with emergency
placement.8 Adequate .prior hydration and a standardtechnique make successful, uncomplicated venipunc-ture more certain. A necessity for active assistedventilation increases the severity and significanceof pleural transgression during the procedure. For-tunately, diagnosis and treatment of potential com-plications are generally straightforward, especiallywhen these problems are anticipated. The significanceof abnormal coagulation is underlined by the reportof a death that was secondary to mediastinal hemor-rhage.3 In the central locations, mechanical con-siderations may make it very difficult to controlbleeding, necessitating reliance on normal bloodcoagulation to avoid problems. Careful selection ofpatients is, therefore, important.For patients in whom insertions does not succeed on
the first attempt, special caution is needed. The in-cidence of serious complications in this group was quitehigh, and included all three hemorrhagic problems.On the basis of this data, no particular side or siteappears to be particularly prone to these complications.Because it has been notoriously difficult to maintain
adequate dressings for jugular catheters, this site hasbeen unpopular for long-term catheterization. Benottiet al.9 have described a satisfactory technique, thesubcutaneous tunnel, for moving the exit site to theinfraclavicular skin, thus avoiding this problem. Thetechnique was also used to isolate the entry site fromopen cervical or tracheotomy wounds. There were no
mechanical or bacteriologic complications associatedwith the catheters so placed.
Catheter Misdirection
Nutritional catheters terminating in veins other thanthe superior vena cava have previously been associatedwith thrombosis,310 as have those which have beenallowed to remain coiled within the lumen.10'11 Themost frequent site associated with catheter mis-direction was the right subclavian (Table 3). Approx-imately one in ten catheters passed into the rightinternal jugular vein; coiling was also three times morelikely to occur on the right. Inappropriately placedcannulae were redirected into the superior vena cavausing stainless steel guidewires, under fluoroscopiccontrol, prior to administration ofhypertonic dextrose.
Accidental or premature removal of the catheter canbest be prevented by a proper suturing technique.This involves immobilization of the proximal, ex-ternal portion of the catheter to prevent side-to-sidemotion, which can gradually lever it out of position.Occlusion secondary to clotting within the plastictube can generally be corrected by flushing it withsaline soon after this occurs. Obviously, a break in
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TABLE 3. Complications of Insertion (165 Subclavian andInternal Jugular Venipunctures)
Ipsilateral Coiled lateralInternal in Sub-Jugular Vein clavian
Right 10 3 2 15Left 3 1 4
the integrity of the catheter itself requires changingthe device to prevent bacterial colonization, airembolus, or loss or solution.
Catheters and Infection (Table 4)
The 2.8% incidence of sepsis from a catheter focusin this series closely parallels current reports fromother institutions. Copeland et al.,12 in 1977, reporteda 1.6% incidence of infection in a series of cancerpatients, specifically evaluated because of a highexpectation of sepsis from other sources. Ryan3reported a 7% incidence of infections, the majoritycoming from that subgroup of catheters with observedprotocol violations, and a 3% incidence of cathetersepsis among those that are properly maintained. In areview of a number of reports on TPN catheter relatedsepsis, Maki5 cited an overall average incidence of 7%.
Catheter colonization is a practical and easily appliedclinical concept, defining a group of catheters whichrequire therapeutic action (removal), and which maybe held responsible for septicemia. Colonization mayoccur either as seeding from distant sources ofbacteremia or as a significant accumulation of or-ganisms along the subcutaneous tract. Maki's tech-nique13 of selective semiquantitative culture shouldprovide for more accurate definition of colonization,the mechanism of its development, and catheter-related sepsis.Of the five patients who became septic in this
series, three died after prolonged septic illness. Nopatient died as a direct result of catheter-related
sepsis; although one patient's death may have beenhastened. Only one patient in the entire populationwas noted to have a white blood cell count of lessthan 1500 cells/mm3 at the outset of nutritionaltherapy; only two of the patients with colonizedcatheters had reactivity to a standard battery ofintradermal recall antigens. This is in comparisonwith the 70% incidence of reactivity seen in thereferral population.14A predominance of coagulase-negative staphylo-
cocci was observed. The more virulent coagulase-positive staphylococcus was associated with cathe-ter-related sepsis in each of three patients. Therewas no fungi cultured from the catheters. Thesebacteriologic findings are consistent with Maki's13premise that the organisms involved are basicallyskin flora. Therefore, close monitoring and care ofthese catheters should minimize the incidence ofcolonization. However, bacteriologic seeding of intra-venous foreign bodies may also occur, and detectioncan be expected to occur more frequently withestablished protocols for satisfactory maintenanceof the insertion site. In fact, two of the five septiccatheters had well documented sources for suchseeding and are presumed to have become colonizedby this mechanism.
TABLE 4. Catheter Related Infection (175Catheters Successfully Placed)*
Per CentNum- Incidenceber of ofPa- Positive Positive
Of the catheters removed because of unexplainedsepsis, fully 85% were not colonized. On the otherhand, all five septic catheters were removed, and thediagnosis was established because of this suspicion.All of the colonized catheters removed for this reason
were eventually shown to be septic. Thus, the valueof changing the catheter and culturing it cannot beoveremphasized.None of the patients with subcutaneous tunneling,
or who had catheters changed over a wire, developedpositive cultures, supporting the acceptability of theseprocedures. Although there appeared to be a moder-ately increased risk of colonization with internaljugular catheters, the outstanding risk was withfemoral venipuncture.Femoral catheters have been avoided for many years
because of an increased incidence of both thrombusformation and infection, complications which were
corroborated here. Allowing the use of a femoral sitefor TPN resulted in two septic catheters, one ap-parently seeded by the other.
Dividing the catheters into subgroups, severalconclusions are suggested. Interpretation of the datamust take into account the statistical implications ofthe relatively small numbers involved.Three subgroups of patients with an increased
incidence of bacteriologic complications were iden-tified. As might be expected, a high incidence was
found in the group of catheters which were "takenover." Although their average duration in situ as
TPN cannulae was shorter, the standard insertion andmaintenance precautions would not have been ob-served during the initial time of their use.
The patients treated with "piggyback" fat emulsionsor cyclic regimens demonstrated a moderately in-creased incidence of colonization. Although this sug-gests a slightly greater risk from these "controlled"violations of standard protocol, other factors need tobe considered as well. For example, two of the threepositive catheter cultures associated with intravenousfat were from the patient with the femoral catheter.
Venous Thrombosis (Table 5)
Clearly, five of the patients developed thrombosissecondary to their TPN catheters. In an additionalfour patients, other invasive devices may also havecontributed to the presence of thrombi. A host offactors have been related to venous thrombosis in thepast, several of which were prominent in this group ofnine patients. Especially notable were prolonged bedrest (all nine patients), sepsis (six patients), con-gestive failure (five patients), and malignant disease(four patients). In addition, all patients underwentprolonged exposure to an intravenous foreign bodydelivering potentially irritating solutions. It is probablethat the reported incidence is falsely low sinceautopsy examinations were performed on only one-halfof the patients who died. In addition, four thrombiobserved at autopsy examinations were not clinicallyapparent. If one were to extrapolate the occultautopsy incidence (four in 19) to the clinical population,a 21% incidence of inapparent thrombotic phenomenawould result.For what is described as a relatively unusual
clinical condition, this complication appears in a re-markable number of patients. In fact, its incidencewas greater than that of significant infection or majorcomplications of placement. It is worth noting thatso-called "effort" (or "spontaneous") axillary orsubclavian vein thrombosis occurs 66% of the time onthe right side. 15 The remarkable initial left-sidedincidence of subclavian thrombosis is even less at-tributable to chance, in light of the predominance ofright-sided catheterization (Table 2). The increasedrisk of thrombosis with left-sided cannulation issignificant at p < 0.01 by chi square analysis using atwo tailed test.
Prevention of this complication can be achieved inseveral ways. The use of less thrombogenic heparin-impregnated7 or silicone16 catheters should be en-couraged. Assiduous avoidance of the femoral siteshould continue. At our institution 6000 units ofheparin per 24 hours is routinely added to thenutritional solutions of some patients and appears toreduce this complication. When a choice is available,nutritional catheterization should be preferentiallyperformed on the right side. While there is a greaterchance of misdirection from the right side this seemsa small price to pay for decreasing the incidenceof thrombosis. Misdirected catheters are easily re-routed but subclavian thrombosis is permanent.
In summary, insertion of a central venous catheterfor parenteral nutrition can be a safe and effectiveprocedure with minimal risk of complications anddeath. The progressive decline of infectious prob-
269Vol. 193 o No. 3
270 PADBERG AND OTHERS Ann. Surg. March 1981
lems3,12'17 emphasizes the need for a precise protocoldelivered by an experienced team. Thus, the patientcan benefit from the prevention or treatment of hospitalmalnutrition, with a minimum of complications.
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